"Easy women get it": pre-existing stigma associated with HPV and cervical cancer in a low-resource setting prior to implementation of an HPV screen-and-treat program.

BACKGROUND: Cervical cancer is preventable with vaccination and early detection and treatment programs. However, for these programs to work as intended, stigma related to HPV and cervical cancer must be understood and addressed. We explored pre-existing stigma associated with HPV and cervical cancer in the public healthcare system and community of a low-resource setting prior to implementation of an HPV screen-and-treat program. METHODS: This study conducted thematic analysis of data collected during implementation of a novel HPV screen-and-treat system for cervical cancer early detection and treatment in Iquitos, Peru. We included 35 semi-structured interviews (19 health professionals, 16 women with cervical precancer or cancer), eight focus groups (70 community women), one workshop (14 health professionals), 210 counseling observations (with 20 nurse-midwives), and a document review. We used the Socio-Ecological Model to organize the analysis. RESULTS: We identified three main themes: 1. the implication that women are to blame for their HPV infection through characterizations of being easy or promiscuous, 2. the implication that men are to blame for women's HPV infections through being considered careless or unfaithful, 3. HPV is shameful, embarrassing, and something that should be hidden from others. Consequently, in some cases, women refrained from getting screened for HPV. These themes were seen at the individual level among women, relationship level among women, men, and family members, community level among healthcare staff, and societal level within components of cervical cancer guidelines and male chauvinism. CONCLUSIONS: Cervical cancer early detection and treatment programs in limited resource settings must address stigma entrenched throughout the entire healthcare system and community in order to sustainably and successfully implement and scale-up new programs. Interventions to tackle this stigma can incorporate messages about HPV infections and latency to lessen the focus on the influence of sexual behavior on HPV acquisition, and instead, promote screening and treatment as paramount preventative measures.

Etiology of acute febrile illness in the peruvian amazon as determined by modular formatted quantitative PCR: a protocol for RIVERA, a health facility-based case-control study.

BACKGROUND: The study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity. We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI. METHODS: A case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21-28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI. DISCUSSION: The modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 h and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific prevalent pathogens as a cause of acute illness. STUDY REGISTRATION: Project 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú.

Resistance to single dose albendazole and reinfection with intestinal helminths among children ages 2 to 11 years from the Peruvian Amazon region: a study protocol.

BACKGROUND: Deworming programs aimed at reducing morbidity and mortality from geohelminth infections are common in many countries where these infections are endemic, but data demonstrating increasing levels of resistance to albendazole and mebendazole are causes for concern. Studies to evaluate the clinical efficacy of deworming programs are critical to maintain high infection control goals. METHODS: We propose to assess the clinical efficacy of Peruvian national guidelines for deworming programs in a prospective observational study conducted in the Amazon River basin area near Iquitos, Peru. Major outcomes to be evaluated include (1) albendazole resistance of intestinal helminths (trichuriasis, ascariasis, hookworm), and (2) frequency of reinfection with intestinal helminths 4 months after treatment with albendazole. Children ages 2-11 years from the Belén District of Iquitos will be identified based on a community census. Following parental informed consent, demographic data, weight, and height will be recorded and a stool specimen for parasitological exam by direct observation and Kato-Katz concentration method, and helminthic egg counts will be collected prior to administration of albendazole, following Peruvian national guidelines. Follow-up stool specimens examined in the same manner will be collected at 20 days, 90 days, and 100 days following initial administration of albendazole, and based on parasites found repeat treatment will be administered in accordance with national guidelines. Real-time multiplex qPCR will be performed on helminth positive samples collected prior to initial deworming and on helminth-positive specimens detected on day 15-20. A total sample size of 380 participants was calculated based on total population in the target group and prevalence estimates of helminth infections and clinical resistance based on recent data. DISCUSSION: Data from observational clinical efficacy studies are important to guide geohelminth infection control programs. Trial registration https://www.researchregistry.com/ . Identification number: researchregistry7736; Registered retrospectively March 13, 2022; https://www.researchregistry.com/browse-the-registry#home/registrationdetails/622e024cf06132001e3327bf/.

Efficacy of Single-Dose Albendazole and Albendazole Plus Ivermectin for Soil-Transmitted Helminth Infection in Children in the Peruvian Amazon.

In countries where soil-transmitted helminth (STH) infections are endemic, deworming programs are recommended to reduce morbidity; however, increasing levels of resistance to benzimidazoles are of concern. In an observational study in Peru, we studied the clinical efficacy of 400 mg of albendazole 20 days after treatment among children aged 2-11 years. Of 426 participants who provided samples, 52.3% were infected with a STH, 144 (33.8%) were positive for Ascaris (41.8% light, 50.8% moderate, and 7.4% heavy infections), 147 (34.5%) were positive for Trichuris (75.2% light, 22.5% moderate, and 2.3% heavy infections), and 1.1% were positive for hookworm species (100% light infections). Additional stool samples were examined at 20, 90, and 130 days after the initial treatment. At 20 days post-administration of albendazole, the cure rate (CR) of Ascaris infection was 80.1% (95% CI: 73.5-86.7), and the egg reduction rate (ERR) was 70.8% (95% CI: 57.8-88.7); the CR for Trichuris infection was 27.1% (95% CI: 20.0-34.3), and the ERR was 29.8% (95% CI: -1.40 to 57.5). Among participants with persistent or recurrent infections with Trichuris, the combined therapy of albendazole (400 mg) and ivermectin at 600 µg/dose increased overall CR for Trichuris infection to 75.2% (95% CI: 67.3-83.2%) with an ERR of 84.2% (95% CI: 61.3-93.8%). Albendazole administration alone for the control of STH was associated with high rates of treatment failure, especially for Trichuris. Combined single doses of albendazole and ivermectin was observed to have improved efficacy.

Dengue and COVID-19 Co-Circulation in the Peruvian Amazon: A Population-Based Study.

The COVID-19 pandemic affected the main Amazon cities dramatically, with Iquitos City reporting the highest seroprevalence of anti-SARS-CoV-2 antibodies during the first COVID-19 wave worldwide. This phenomenon raised many questions about the possibility of a co-circulation of dengue and COVID-19 and its consequences. We carried out a population-based cohort study in Iquitos, Peru. We obtained a venous blood sample from a subset of 326 adults from the Iquitos COVID-19 cohort (August 13-18, 2020) to estimate the seroprevalence of anti-dengue virus (DENV) and anti-SARS-CoV-2 antibodies. We tested each serum sample for anti-DENV IgG (serotypes 1, 2, 3, and 4) and SARS-CoV-2 antibodies anti-spike IgG and IgM by ELISA. We estimated an anti-SARS-CoV-2 seroprevalence of 78.0% (95% CI, 73.0-82.0) and an anti-DENV seroprevalence of 88.0% (95% CI, 84.0-91.6), signifying a high seroprevalence of both diseases during the first wave of COVID-19 transmission in the city. The San Juan District had a lower anti-DENV antibody seroprevalence than the Belen District (prevalence ratio, 0.90; 95% CI, 0.82-0.98). However, we did not observe these differences in anti-SARS-CoV-2 antibody seroprevalence. Iquitos City presented one of the highest seroprevalence rates of anti-DENV and anti-SARS-CoV-2 antibodies worldwide, but with no correlation between their antibody levels.

"Easy women get it": Pre-existing stigma associated with HPV and cervical cancer in a low-resource setting prior to implementation of an HPV screen-and-treat program.

Background: Cervical cancer is preventable with vaccination and early detection and treatment programs. However, in order for these programs to work as intended, stigma related to HPV and cervical cancer must be understood and addressed. We explored pre-existing stigma associated with HPV and cervical cancer in the public healthcare system of a low-resource setting prior to implementation of an HPV screen-and-treat program. Methods: This study conducted thematic analysis of data collected during implementation of a novel HPV screen-and-treat system for cervical cancer early detection and treatment in Iquitos, Peru. We included 35 semi-structured interviews (19 health professionals, 16 women with cervical precancer or cancer), eight focus groups (70 community women), one workshop (14 health professionals), 210 counseling observations (with 20 nurse-midwives), and a document review. We used the Socio-Ecological Model to organize the analysis. Results: We identified three main themes: 1. the implication that women are to blame for their HPV infection through characterizations of being easy or promiscuous, 2. the implication that men are to blame for women's HPV infections through being considered careless or unfaithful, 3. HPV is shameful, embarrassing, and something that should be hidden from others. Consequently, in some cases, women refrained from getting screened for HPV. These themes were seen at the individual level among women, relationship level among women, men, and family members, community level among healthcare staff, and societal level within components of cervical cancer guidelines and male chauvinism. Conclusions: Cervical cancer early detection and treatment programs in limited resource settings must address stigma entrenched throughout the entire healthcare system in order to sustainably and successfully implement and scale-up new programs. Interventions to tackle this stigma can incorporate messages about HPV infections and latency to lessen the focus on the influence of sexual behavior on HPV acquisition, and instead, promote screening and treatment as paramount preventative measures.

Feasibility of Training Community Health Workers to Use Smartphone-Attached Microscopy for Point-of-Care Visualization of Soil-Transmitted Helminths in the Peruvian Amazon.

The prevalence of soil-transmitted helminths (STH) is high in communities within the Peruvian Amazon despite repeated mass-drug administration, demanding alternative strategies of control. Smartphone-attached microscopy (SAM) permits visualization of STH from a small portable microscope through a smartphone screen, potentially providing an inexpensive and rapid method of STH visualization in communities where diagnostic laboratories with microscopes are inaccessible. In this study, a total of 45 community health workers who work within the health systems of Loreto, Peru, attended a 1-day training session with lectures and practicums on STH and SAM. Participants received a pre- and post-intervention questionnaire. Post-intervention, participants were significantly more confident using SAM and identifying parasite images, symptoms, transmission, and treatment (P ≤ 0.0045). Post-intervention, participants correctly labeled a median of five of seven SAM apparatus components and five of eight steps of Kato-Katz technique, were less likely to choose taking medicine to prevent parasite infection (P = 0.0075), and were more likely to select Kato-Katz technique as a type of diagnostic test (P < 0.0001). Most participants felt ready to use SAM in their communities and stated that it could help rural communities far from health centers or laboratories (24%); provide faster identification, results, diagnosis (19%); permit at-home or on-the-spot visualization (14%); and save money (14%). Results show that community health workers show a high level of willingness and competency to learn about both STH and SAM and may be a yet-unexplored practical method of augmenting STH visualization, bringing healthcare to communities in Loreto with poor access to diagnostic laboratories and clinics.

Etiology of Acute Febrile Illness in the Peruvian Amazon as determined by modular formatted quantitative PCR: A Protocol for RIVERA, a Health Facility-Based Case-Control Study.

Background: The study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity. We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI. Methods: A case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21-28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI. Discussion: The modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 hours and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific, prevalent pathogens as a cause of acute illness. Study Registration: Project 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú.

Seroprevalence of anti-SARS-CoV-2 antibodies in Iquitos, Peru in July and August, 2020: a population-based study.

BACKGROUND: Detection of anti-SARS-CoV-2 antibodies among people at risk of infection is crucial for understanding both the past transmission of COVID-19 and vulnerability of the population to continuing transmission and, when done serially, the intensity of ongoing transmission over an interval in a community. We aimed to estimate the seroprevalence of COVID-19 in a representative population-based cohort in Iquitos, one of the regions with the highest mortality rates from COVID-19 in Peru, where a devastating number of cases occurred in March, 2020. METHODS: We did a population-based study of SARS-CoV-2 transmission in Iquitos at two timepoints: July 13-18, 2020 (baseline), and Aug 13-18, 2020 (1-month follow-up). We obtained a geographically stratified representative sample of the city population using the 2017 census data, which was updated on Jan 20, 2020. We included people who were inhabitants of Iquitos since COVID-19 was identified in Peru (March 6, 2020) or earlier. We excluded people living in institutions, people receiving any pharmacological treatment for COVID-19, people with any contraindication for phlebotomy, and health workers or individuals living with an active health worker. We tested each participant for IgG and IgM anti-SARS-CoV-2 antibodies using the COVID-19 IgG/IgM Rapid Test (Zhejiang Orient Gene Biotech, China). We used survey analysis methods to estimate seroprevalence accounting for the sampling design effect and test performance characteristics. FINDINGS: We identified 726 eligible individuals and enrolled a total of 716 participants (99%), distributed across 40 strata (four districts, two sexes, and five age groups). We excluded ten individuals who: did not have consent from a parent or legal representative (n=3), had moved to Iquitos after March 6, 2020 (n=3), were in transit (n=2), or had respiratory symptoms (n=1). After adjusting for the study sampling effects and sensitivity and specificity of the test, we estimated a seroprevalence of 70% (95% CI 67-73) at baseline and 66% (95% CI 62-70) at 1 month of follow-up, with a test-retest positivity of 65% (95% CI 61-68), and an incidence of new exposures of 2% (95% CI 1-3). We observed significant differences in the seroprevalence between age groups, with participants aged 18-29 years having lower seroprevalence than those aged younger than 12 years (prevalence ratio 0·85 [95% CI 0·73-0·98]; p=0·029). INTERPRETATION: After the first epidemic peak, Iquitos had one of the highest rates of seroprevalence of anti-SARS-CoV-2 antibodies worldwide. Nevertheless, the city experienced a second wave starting in January, 2021, probably due to the emergence of the SARS-CoV-2 P1 variant, which has shown higher transmissibility and reinfection rates. FUNDING: Dirección Regional de Salud de Loreto (DIRESA), Loreto, Peru. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Safety of Lactobacillus Reuteri DSM 17938 in Healthy Children 2-5 Years of Age.

Probiotics are increasingly used for diarrhea, but studies under the Food and Drug Administration and Investigational New Drug program are few. We conducted a phase-one placebo-controlled study of Lactobacillus reuteri DSM 17938 under Investigational New Drug program in 60 children 2-5 years of age (41 L. reuteri, 19 placebos) in a resource-constrained community in Peru. No differences in objective data on adverse events were noted, although some differences based on subjective parental reports for fever and diarrhea were seen.

The other Campylobacters: Not innocent bystanders in endemic diarrhea and dysentery in children in low-income settings.

BACKGROUND: Campylobacter is one of the main causes of gastroenteritis worldwide. Most of the current knowledge about the epidemiology of this food-borne infection concerns two species, C. coli and C. jejuni. Recent studies conducted in developing countries and using novel diagnostic techniques have generated evidence of the increasing burden and importance of other Campylobacter species, i.e. non-C. coli/jejuni. We performed a nested case-control study to compare the prevalence of C. coli/jejuni and other Campylobacter in children with clinical dysentery and severe diarrhea as well as without diarrhea to better understand the clinical importance of infections with Campylobacter species other than C. coli/jejuni. METHODOLOGY/PRINCIPAL FINDINGS: Our nested case-control study of 439 stool samples included dysenteric stools, stools collected during severe diarrhea episodes, and asymptomatic stools which were systematically selected to be representative of clinical phenotypes from 9,160 stools collected during a birth cohort study of 201 children followed until two years of age. Other Campylobacter accounted for 76.4% of the 216 Campylobacter detections by qPCR and were more prevalent than C. coli/jejuni across all clinical groups. Other Campylobacter were also more prevalent than C. coli/jejuni across all age groups, with older children bearing a higher burden of other Campylobacter. Biomarkers of intestinal inflammation and injury (methylene blue, fecal occult test, myeloperoxidase or MPO) showed a strong association with dysentery, but mixed results with infection. MPO levels were generally higher among children infected with C. coli/jejuni, but Shigella-infected children suffering from dysentery recorded the highest levels (26,224 ng/mL); the lowest levels (10,625 ng/mL) were among asymptomatic children infected with other Campylobacter. Adjusting for age, sex, and Shigella infection, dysentery was significantly associated with C. coli/jejuni but not with other Campylobacter, whereas severe diarrhea was significantly associated with both C. coli/jejuni and other Campylobacter. Compared to asymptomatic children, children suffering from dysentery had a 14.6 odds of C. coli/jejuni infection (p-value < 0.001, 95% CI 5.5-38.7) but were equally likely to have other Campylobacter infections-odds ratio of 1.3 (0.434, 0.7-2.4). Children suffering from severe diarrhea were more likely than asymptomatic children to test positive for both C. coli/jejuni and other Campylobacter-OR of 2.8 (0.034, 1.1-7.1) and 1.9 (0.018, 1.1-3.1), respectively. Compared to the Campylobacter-free group, the odds of all diarrhea given C. coli/jejuni infection and other Campylobacter infection were 8.8 (<0.001, 3.0-25.7) and 2.4 (0.002, 1.4-4.2), respectively. Eliminating other Campylobacter in this population would eliminate 24.9% of the diarrhea cases, which is almost twice the population attributable fraction of 15.1% due to C. coli/jejuni. CONCLUSIONS/SIGNIFICANCE: Eighty-seven percent of the dysentery and 59.5% of the severe diarrhea samples were positive for Campylobacter, Shigella, or both, emphasizing the importance of targeting these pathogens to limit the impact of dysentery and severe diarrhea in children. Notably, the higher prevalence of other Campylobacter compared to C. coli/jejuni, their increasing burden during early childhood, and their association with severe diarrhea highlight the importance of these non-C. coli/jejuni Campylobacter species and suggest a need to clarify their importance in the etiology of clinical disease across different epidemiological contexts.

"We need people to collaborate together against this disease": A qualitative exploration of perceptions of dengue fever control in caregivers' of children under 5 years, in the Peruvian Amazon.

BACKGROUND: Dengue Fever presents a significant and growing burden of disease to endemic countries, where children are at particular risk. Worldwide, no effective anti-viral treatment has been identified, thus vector control is key for disease prevention, particularly in Peru where no vaccine is currently available. This qualitative study aimed to explore the perceptions of dengue control in caregivers' of children under 5 years in Peru, to help direct future mosquito control programmes and strategy. METHODS: Eighteen semi-structured interviews were conducted in one health centre in Iquitos, Peru. Interviews were audio-recorded, transcribed and translated by an independent translator. Data were analysed using an inductive thematic approach. FINDINGS: Three core analytic themes were interpreted: (1) awareness of dengue and its control, (2) perceived susceptibility of children, rural riverside communities and city inhabitants, and (3) perceived responsibility of vector control. Participants were aware of dengue symptoms, transmission and larvae eradication strategies. Misconceptions about the day-time biting behaviour of the Aedes aegypti mosquito and confusion with other mosquito-borne diseases influenced preventative practice. Community-wide lack of cooperation was recognised as a key barrier. This was strengthened by attitudes that the government or health centre were responsible for dengue control and a belief that the disease cannot be prevented through individual actions. Participants felt powerless to prevent dengue due to assumed inevitability of infection and lack of faith in preventative practices. However, children and rural communities were believed to be most vulnerable. CONCLUSIONS: Perceptions of dengue control amongst caregivers to under 5's were important in shaping their likelihood to participate in preventative practices. There is a need to address the perceived lack of community cooperation through strategies creating a sense of ownership of community control and enhancing social responsibility. The belief that dengue cannot be prevented by individual actions in a community also warrants attention. Specific misconceptions about dengue should be addressed through the community health worker system and further research directed to identify the needs of certain vulnerable groups.

Relaciones sexuales y gestación / Sexual relations and pregnancy

Objetivo: Precisar el comportamiento de la gestante respecto a las relaciones sexuales. Diseño: estudio prospectivo en 260 puérperas inmediatas atendidas en el Departamento de Gineco-Obstetricia del Hospital Regional de Loreto, mediante una encuesta aplicada por dos internas de obstetricia capacitadas previamente. Resultados: el 7,3 por ciento era menor de 15 años, 27,3 por ciento tuvo entre 15 y 19 años, el 57,3 por ciento entre 20 y 35 años y el 8,1 por ciento era mayor de 35 años. El 54 por ciento era multípara y el 46 por ciento primípara. El 92,4 por ciento inició sus relaciones sexuales antes de los 20 años. El 59,6 por ciento tuvo más de 2 relaciones al mes durante la primera mitad del embarazo y sólo el 34,6 por ciento durante la segunda mitad. El 87,3 por ciento disminuyó su frecuencia de relaciones sexuales respecto a su etapa pregravídica y el 70 por ciento presentó disminución de la libido; 17,7 por ciento tenía miedo de dañar al feto con las relaciones sexuales. En la segunda mitad del embarazo el 41 por ciento prefirió la posición de costado y el 12,7 por ciento practicó el felatio y el cunnilingus. El 41,2 por ciento contestó que su orgasmo había disminuido. El 24,6 por ciento reconoció que se masturbaba durante la gestación. El 11,5 por ciento tuvo su última relación sexual dentro de la semana antes del parto y el 17,7 por ciento dentro del mes antes del mismo. Conclusiones: durante el embarazo disminuyen la libido, la frecuencia de relaciones sexuales y el orgasmo. También existen cambios de posición en la segunda mitad de la gestación. Se recomienda proporcionar información a la gestante sobre las relaciones sexuales durante la gestación.