Women In Resource-limited Settings Research Articles

Self-supervised learning-based cervical cytology for the triage of HPV-positive women in resource-limited settings and low-data regime

Screening Papanicolaou test samples has proven to be highly effective in reducing cervical cancer-related mortality. However, the lack of trained cytopathologists hinders its widespread implementation in low-resource settings. Deep learning-assisted telecytology diagnosis emerges as an appealing alternative, but it requires the collection of large annotated training datasets, which is costly and time-consuming. In this paper, we demonstrate that the abundance of unlabeled images that can be extracted from Pap smear test whole slide images presents a fertile ground for self-supervised learning methods, yielding performance improvements compared to off-the-shelf pre-trained models for various downstream tasks. In particular, we propose Cervical Cell Copy-Pasting (C3P) as an effective augmentation method, which enables knowledge transfer from public and labeled single-cell datasets to unlabeled tiles. Not only does C3P outperforms naive transfer from single-cell images, but we also demonstrate its advantageous integration into multiple instance learning methods. Importantly, all our experiments are conducted on our introduced in-house dataset comprising liquid-based cytology Pap smear images obtained using low-cost technologies. This aligns with our long-term objective of deep learning-assisted telecytology for diagnosis in low-resource settings.

Model-based predictions of protective HIV pre-exposure prophylaxis adherence levels in cisgender women

Most human immunodeficiency virus (HIV) infections occur in cisgender women in resource-limited settings. In women, self-protection with emtricitabine/tenofovir disoproxil fumarate pre-exposure prophylaxis (FTC/TDF-PrEP) constitutes a major pillar of HIV prevention. However, clinical trials in women had inconsistent outcomes, sparking uncertainty about adherence requirements and reluctance in evaluating on-demand regimens. We analyzed data from published FTC/TDF-PrEP trials to establish efficacy ranges in cisgender women. In a ‘bottom-up’ approach, we modeled hypotheses in the context of risk-group-specific, adherence–efficacy profiles and challenged those hypotheses with clinical data. We found that different clinical outcomes were related to the proportion of women taking the product, allowing coherent interpretation of the data. Our analysis showed that 90% protection was achieved when women took some product. We found that hypotheses of putative male/female differences were either not impactful or statistically inconsistent with clinical data. We propose that differing clinical outcomes could arise from pill-taking behavior rather than biological factors driving specific adherence requirements in cisgender women.

Quantifying differences in iron deficiency-attributable anemia during pregnancy and postpartum

Pregnant women in resource-limited settings are highly susceptible to anemia and iron deficiency, but the etiology of postpartum anemia remains poorly defined. To inform the optimal timing for anemia interventions, changes in iron deficiency-attributable anemia through pregnancy and postpartum need to be understood. In 699 pregnant Papua New Guinean women attending their first antenatal care appointment and following up at birth and 6 and 12months postpartum, we undertake logistic mixed-effects modeling to determine the effect of iron deficiency on anemia and population attributable fractions, calculated from odds ratios, to quantify the contribution of iron deficiency to anemia. Anemia is highly prevalent during pregnancy and 12months postpartum, with iron deficiency increasing the odds of anemia during pregnancy and, to a lesser extent, postpartum. Iron deficiency accounts for ≥72% of anemia during pregnancy and 20%-37% postpartum. Early iron supplementation during and between pregnancies could break the cycle of chronic anemia in women of reproductive age.

Congenital Infections: Priorities and Possibilities for Resource-limited Settings.

Congenital infections are an under-recognized cause of morbidity and mortality in resource-limited settings (RLS). The “SCORTCH” acronym highlights the range of congenital infections: Syphilis, Cytomegalovirus (CMV), “Other” (eg, Zika, malaria, Chagas disease, parvovirus, enterovirus), Rubella, Toxoplasmosis, Chickenpox, and all the H’s, Herpes simplex virus (HSV), HIV, Hepatitis B and C, Human T-lymphotropic virus-1.1 Clinical severity depends on a range of factors, including timing of infection, pathogenicity of strain, and the relative maturity of the fetal/maternal immune system. Most infections are asymptomatic in the mother and neonate. In high-income countries (HICs), screening programs, routine obstetric and neonatal care, specific treatments and vaccination have reduced the incidence of congenital infections. However, these interventions are often not available in RLS. Moreover, in the absence of population-based surveillance and limited laboratory testing capacity, it is likely that the burden of undiagnosed congenital infections is higher in RLS. Public health strategies and interventional programs could have a huge impact on reducing congenital infections in these settings. This review focuses on the priorities and possibilities for managing congenital syphilis, CMV and HSV. CONGENITAL SYPHILIS Mother-to-child transmission of syphilis can lead to a wide spectrum of complications including stillbirth, neonatal death and symptomatic infant infection (Table 1). In 2016, the global congenital syphilis rate was 473 cases/100,000 livebirths, substantially higher than the WHO target of 50 of 100,000.2 An estimated 1 million women worldwide live with syphilis, with the highest burden in sub-Saharan Africa. A 2007 WHO framework highlighted the need to improve political advocacy, antenatal healthcare services, screening and surveillance to eliminate congenital syphilis (https://www.who.int/publications/i/item/the-global-elimination-of-congenital-syphilis-rationale-and-strategy-for-action). However, in 2017, the WHO and the Gates Foundation reported that little progress had been made, mainly due to stigma, difficulty capturing cases related to stillbirth, limited access to benzathine benzylpenicillin, and a lack of coordinated responses across agencies. A WHO global progress report in 2020 showed that 95% coverage of antenatal screening for HIV and syphilis was achieved in only 70% of countries (https://www.who.int/publications/i/item/9789240027077). Improving accessibility to a range of public health measures could enable an immediate reduction in the burden of congenital syphilis in RLS. TABLE 1. - Clinical Presentations of Neonates with Symptomatic Congenital Infections Syphilis CMV HSV Prematurity Yes Yes Yes Low birth weight Yes Yes Yes Lymphadenopathy Yes No No Hepatosplenomegaly Yes Yes Yes (disseminated HSV) Jaundice (may be conjugated) Yes Yes Yes (disseminated HSV) Hepatitis Yes Yes Yes (disseminated HSV) Anemia Yes Yes Yes (disseminated HSV) Thrombocytopenia Yes Yes Yes (disseminated HSV) White blood count High or low Normal or low Normal or low Hearing Sensorineural deafness Sensorineural deafness N/A Skeletal Osteochondritis, periostitis N/A N/A Renal Glomerulonephritis, nephrotic syndrome N/A N/A Pneumonitis Yes Yes Yes (disseminated HSV) Central nervous system Meningitis, microcephaly, hydrocephaly, intracranial calcification microcephaly, ventriculomegally, cysts, polymicrogyria, abnormal white matter, intracranial calcification Encephalitis, meningitis Eyes Cataracts, corneal scarring, glaucoma, chorioretinitis, microphthalmia. Retinal scarring, chorioretinitis Keratitis/corneal scarring in all forms of HSV disease Rash Usually maculopapular, but any possible, including blueberry muffin rashPalms and soles may be red, mottled and swollenSevere desquamation of hands/feet is pathognomonicVesiculobullous lesions, condylomata lata in moist areas/perioral fissures Rare, may have blueberry muffin rash Vesicular/ulcerative lesions N/A, not applicable. PUBLIC HEALTH MEASURES WHO has outlined a pathway to the elimination of mother-to-child transmission of syphilis (https://www.who.int/publications/i/item/9789240039360). To achieve the targets of <50 cases/100,000, at least 1 dual HIV/syphilis test should be conducted in the first trimester to facilitate early antenatal treatment. Dual testing assays are cheap, highly sensitive and produce rapid results, and WHO ultimately aims to include hepatitis B surface antigen as a triple test. Intramuscular benzathine penicillin at least 30 days before delivery remains the gold standard for treatment of syphilis in pregnancy, but a WHO target of >95% coverage of one dose for syphilis-seropositive pregnant women has yet to be achieved in part due to shortages in the production and distribution of benzathine penicillin. Oral options such as amoxicillin and cefixime may be more readily available alternatives, but their efficacy in randomized trials merit further investigation.3 CONGENITAL CMV Congenital CMV (cCMV) is the most common nongenetic cause of sensorineural hearing loss. Congenital infection also causes neurodevelopmental impairment in 20% of infants. A meta-analysis, including 23 and 54 studies from RLS and HIC settings respectively, found a 3-fold higher birth prevalence of cCMV in RLS (1.4%) compared with HIC (0.5%).4 Population risk factors for cCMV include maternal CMV and HIV seroprevalence and younger maternal age. Compared with HIC, CMV in RLS is usually acquired earlier in life; CMV seroprevalence in adulthood is close to 100% in sub-Saharan Africa, in contrast to 58% seroprevalence among women of childbearing age in the United States.5 Almost all pregnant women in sub-Saharan Africa are therefore CMV seropositive, but it is active, replicating CMV (defined as detectable CMV DNA in plasma, urine or saliva) that is associated with mother-to-child transmission, which may occur at initial infection, through viral reactivation, or after reinfection with a different strain. Transmission is more likely in the small proportion of women who acquire primary infection during pregnancy, but the infant can be as severely affected whether the mother is already CMV seropositive or seroconverts during pregnancy. CMV transmission in the first/early second trimester is associated with the most severe end-organ damage. In symptomatic neonates, 6 months of oral valganciclovir, started within the first month of life, has a modest impact on preventing hearing deterioration and improving neurodevelopmental outcomes. However, valganciclovir is not available in most RLS. Reducing the burden of cCMV therefore relies upon measures to reduce transplacental transmission through a range of hygiene measures during the antenatal period. ANTENATAL HYGIENE MEASURES A systematic review evaluating hygiene measures during pregnancy in HIC found that a range of behavioral and education measures could reduce CMV seroconversion during pregnancy.6 Improving antenatal water, sanitation and hygiene (WASH) may therefore prevent cCMV secondary to maternal reinfection, but would likely have no impact on congenital infection through maternal CMV reactivation. CMV VACCINES Studies of vaccine candidates, mainly aimed to protect against infection in solid organ transplant recipients, have been on-going for 40 years. In congenital infection, the aim of vaccination is not to create sterilizing immunity in the mother but to prevent transplacental transmission. In seropositive women, a CMV vaccine would need to generate sufficient antibody and T-cell responses to prevent fetal infection. There are close relationships between CMV, HIV and tuberculosis, so the indirect protective effects of a CMV vaccine on reducing the burden of these infections in RLS may be an important additional benefit.7 A phase III trial in the United States is evaluating safety and efficacy of an mRNA candidate vaccine in women of childbearing age (https://clinicaltrials.gov/ct2/show/NCT05085366). The primary outcome measure is seroconversion in seronegative women. The applicability of such a trial in RLS is unclear given the rarity of CMV seronegativity and the cold-chain storage requirements of mRNA vaccines. An immediate research priority should be the development of an international congenital CMV registry to capture robust epidemiologic data to inform vaccine trials and to evaluate vaccine effectiveness in seropositive women in RLS. NEONATAL HSV Neonatal HSV has 3 phenotypes: skin eye mouth, central nervous system and disseminated disease, with up to 30% mortality in the latter syndrome. The majority of cases occur after exposure in the genital tract at delivery, and the highest risk for transmission occurs for neonates born to women with recent primary infection. A WHO global estimate of the burden of neonatal HSV concluded that approximately a third of all neonatal HSV cases occurred in Africa are due to a high incidence of HSV-2, although this may be an underestimate due to poor quality surveillance data. Observational data from South Africa showed that genital HSV-2 shedding at delivery among HSV-seropositive women living with HIV was almost twice as high as among HSV-seropositive women without HIV (23% vs. 12%), suggesting a higher burden of neonatal HSV in HIV endemic regions.8 BEHAVIORAL STRATEGIES A range of preventive measures, including suppressive acyclovir in late pregnancy, selective cesarean sections, and careful obstetric care at delivery to identify genital lesions all rely on well-funded antenatal and peripartum care. Ideally, a premembrane rupture cesarean section should be undertaken in women with active genital herpes lesions to prevent transmission. However, neonatal HSV infection often occurs in the absence of genital lesions, and surgery often carries inherent risks in RLS, changing the risk-benefit balance in RLS compared with HIC. Preventing maternal HSV acquisition through sex education may reduce the burden of disease. Recent WHO guidance reiterates the importance of not engaging in sexual activity if genital lesions are present, and this is especially important in late pregnancy when the risk of neonatal HSV is highest (https://www.who.int/news-room/fact-sheets/detail/herpes-simplex-virus). Pregnant women with genital lesions should undergo HSV, HIV and syphilis testing. HSV MICROBICIDES AND VACCINES Microbicides applied topically to the vagina and/or rectum offer some protection against primary HSV. In a trial of 422 HSV-2-seronegative South African women, pericoital tenofovir gel halved seroconversion (10.2/100-person-years vs. 21.0/100-person-years) and reached higher concentrations than oral preparations.9 In vitro studies have demonstrated novel microbicide candidates with dual protection against HIV-1 and HSV-2, but efficacy trials are required. There are no licensed HSV vaccines, but several candidates are in preclinical and phase I/II trials.10 A prophylactic vaccine would prevent transmission and active infection, indirectly preventing latent infection and reactivation. As with human papilloma virus, prophylactic vaccination should occur before sexual debut. A therapeutic vaccine would prevent severe complications of HSV in seropositive recipients. Again, a disease registry is crucial to capture the burden of neonatal HSV infection and impact of vaccination. CONCLUSION Syphilis, CMV and HSV can cause catastrophic illness in the newborn, and the long-term burden of these infections in RLS remains unknown. Surveillance studies are required to elucidate the consequences of congenital infections and will help inform preventive strategies. Vaccine trials designed for RLS must consider context-specific factors including: antenatal seroprevalence, maternal and infant immunity, HIV prevalence, capacity for cold chain storage and availability of antivirals. Disease registries which capture epidemiologic trends, assess long-term neurodevelopmental outcomes, and act as an opportunity to conduct interventional studies could be modeled on existing HIV surveillance frameworks (https://www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/hiv/strategic-information/hiv-surveillance). Population-based data could better inform the health economic cost of managing infants with congenital infections, and potential benefits of interventions. Overall, the promotion of holistic, nonstigmatizing pregnancy care is essential to support women in RLS and protect infants from congenital infections.

WITHDRAWN: Early identification of hypertensive disorders of pregnancy (An mhealth feasibility study for resource limited settings)

Hypertensive Disorders of Pregnancy (HDP) account for 18% of potential preventable maternal deaths in South Africa. MHealth studies on early HDP identification in high income countries showed potential value for limited resource settings. This study aimed to test the feasibility of an mHealth solution for early identification of HDP using self home monitoring of blood pressure (BP) and sharing of information on symptoms of preeclampsia in a low middle income country (LMIC). This mixed methods study, enrolled 100 pregnant women (20 to 30 weeks) to selfmonitor and submit daily BP and pulse readings on a smart phone to an mHealth platform observed by a midwife for targeted action. Information was shared on 7 symptoms of preeclampsia using brochures, posters, targeted digital messages and quizzes. Study data was collected through the mHealth platform, key informant interviews, pre pand post knowledge, attitude and practice (KAP) suveys and self and community health worker’s (CHW) reported outcomes. Ten cases had interventions for HDP in the cohort. All mothers with HDP and their babies had satisfactory outcomes. This was facilitated through the BP monitoring on the App and digital platform, increased knowledge of 7 symptoms of preeclampsia and CHW follow up. The study found in conclusion that pregnant women in resource limited settings are able to self home monitor their BP using a mHealth solution for early identification and management of HDP. The study acknowledge challenges for scale up and cost effectiveness but recognise potential.

A simple guide to ultrasound screening for placenta accreta spectrum for improving detection and optimizing management in resource limited settings.

Placenta accreta spectrum is a pregnancy complication associated with severe morbidity and maternal mortality especially when not suspected antenatally and appropriate management instigated. Women in resource-limited settings are more likely to face adverse outcomes due to logistic, technical, and resource inadequacies. Accurate prenatal imaging is an important step in ensuring good outcomes because it allows adequate preparation and an appropriate management approach. This article provides a simple three-step approach aimed at guiding clinicians and sonographers with minimal experience in placental accreta spectrum through risk stratification and basic prenatal screening for this condition both with and without Doppler ultrasound.

Birth preparedness and complication readiness among pregnant women in resource-limited setting in rural Northern Ghana

Birth preparedness and complication readiness among pregnant women in resource-limited setting in rural Northern Ghana

Highly Sensitive and Rapid Identification of Streptococcus agalactiae Based on Multiple Cross Displacement Amplification Coupled With Lateral Flow Biosensor Assay.

Streptococccus agalactiae (S. agalactiae) is an important neonatal pathogen that is associated with mortality and morbidity. Therefore, we developed a rapid, accurate, and sensitive method based on multiple cross displacement amplification (MCDA) for the detection of the target pathogen. Four sets of MCDA primers were designed for targeting the S. agalactiae-specific groEL gene, and one set of MCDA primers with the optimum amplification efficiency was screened for establishing the S. agalactiae-MCDA assay. As a result, the newly-developed assay could be conducted at a fixed temperature (61°C) for only 30 min, eliminating the use of complex instruments. A portable and user-friendly nanoparticle-based lateral flow biosensor (LFB) assay was employed for reporting MCDA results within 2 min. Our results suggested that the detection limit of the S. agalactiae-MCDA-LFB assay is 300 fg per reaction, and no cross-reaction occurred with non-S. agalactiae strains. For 260 vaginal and rectal swabs, the detection rate of the MCDA-LFB assay was 7.7%, which was in accordance with the reference method of enrichment/qPCR, and higher by 4.6% than the CHROMagar culture. Moreover, the total procedure time of the MCDA-LFB assay was around 50 min, including sample collection, template preparation, MCDA reaction, and result reporting. Therefore, the MCDA-LFB assay is superior to enrichment/qPCR and CHROMagar culture and has great promise for point-of-care testing of S. agalactiae from vaginal and rectal swabs of pregnant women in resource-limited settings.

1064 Sleep Patterns Among Urban Haitian Earthquake Survivors Who Experienced the Trauma of Nonpartner Sexual Violence: A Latent Class Analysis Approach

Abstract Introduction Sleep health is crucial to recovery from trauma. Haiti’s Cité Soleil residents (approximately 350,000) live in extreme poverty and regularly experience or witness life-threatening events, including gang and non-partner sexual violence (NPSV). Differences in levels of sleep disturbance among men and women in resource-limited settings who survive disasters as well as NPSV are understudied. In a larger study in which we investigated trauma symptoms among 2010 Haiti earthquake survivors via the Trauma-symptom checklist -40 (N=526; 290 males, 236 females), we also assessed self-reported frequency of sleep disturbance symptoms using the measure’s sleep disturbance subscale, comparing the latter by NPSV victim status and by gender. Methods SAS enabled 3-Class Latent Class Analysis (LCA): Class 1 (“No symptoms”), Class 2 (“Some symptoms”), Class 3 (“All Symptoms)”. Results Distribution of class membership differed by gender (χ2 = 23.9, df = 2, p &amp;lt; .0001). Proportions of respondents assigned to the three classes differed between genders (Females: Class 1, 29.2%; Class 2, 35.5%; Class 3, 35.3%); Males: Class 1, 25.7%; Class 2, 54.4%; Class 3, 19.9%). NPSV status influenced levels of sleep disturbance symptoms, and membership distribution differed across classes by gender (χ2 = 23.9, df = 2, p &amp;lt; .0001). Class 2 membership was greater for men (65.9%), but class 3 membership was greater for women (59.3%). Women who experienced NPSV were statistically more likely members of sleep disturbance symptom classes (Class 2 or Class 3) than Class 1 (χ2= 14.9, df = 2, p = 0.0006). No difference was found in Class membership for men reporting NPSV (χ2= 1.6, df = 2, p = 0.45). Conclusion Investigating the sleep health of Cité Soleil residents adds to the body of literature on sleep health, sleep equity and gendered vulnerability. Findings suggest women in post-disaster settings, especially in LMICs, are at even greater risk for a variety of adverse health outcomes and for suboptimal sleep, even when local men have similar traumatogenic experiences, such as NPSV. Girls and women in post-disaster LMIC settings need trauma-informed sleep health promotion and NPSV-prevention. Support N/A

Feasibility and effect of life skills building education and multiple micronutrient supplements versus the standard of care on anemia among non-pregnant adolescent and young Pakistani women (15\u201324\xa0years): a prospective, population-based cluster-randomized trial

BackgroundAdolescence is a critical period for physical and psychological growth and development, and vitamin and mineral requirements are correspondingly increased. Health and health behaviours correspond strongly from adolescence to adulthood. Developing a preconception care package for adolescent and young women in resource-limited settings could serve to empower them to make informed decisions about their nutrition, health, and well-being, as well as function as a platform for the delivery of basic nutrition-related interventions to address undernutrition.MethodsIn this population-based two-arm, cluster-randomized, controlled trial of life skills building education (provided bi-monthly) and multiple micronutrient supplementation (provided twice-weekly; UNIMMAP composition), we aim to evaluate the effectiveness of the intervention on the prevention of anemia (hemoglobin concentration < 12 g/dL) among adolescent and young women (15–24 years) in Matiari district, Pakistan compared to the standard of care. Several secondary objectives related to nutrition (anthropometry [height, weight, middle upper arm circumference (MUAC)], nutritional status [iron, vitamin A, vitamin D]); general health (morbidity, mortality); and empowerment (age at marriage, completion of the 10th grade, use of personal hygienic materials during menstruation) will also be assessed. Participants will be enrolled in the study for a maximum of 2 years.DiscussionEmpowering adolescent and young women with the appropriate knowledge to make informed and healthy decisions will be key to sustained behavioural change throughout the life-course. Although multiple micronutrient deficiencies are known to exist among adolescent and young women in low-resource settings, recommendations on preconception multiple micronutrient supplementation do not exist at this time. This study is expected to offer insight into providing an intervention that includes both education and supplements to non-pregnant adolescent and young women for a prolonged duration of time within the existing public health programmatic context.Trial registrationThis study is part of the Matiari emPowerment and Preconception Supplementation (MaPPS) Trial. The MaPPS Trial was registered retrospectively on clinicaltrials.gov (Identifier: NCT03287882) on September 19, 2017.

Study protocol on criterion validation of Edinburgh Postnatal Depression Scale (EPDS), Patient Health Questionnaire (PHQ-9) and Centre for Epidemiological Studies-Depression (CES-D) screening tools among rural postnatal women; a cross-sectional study

BackgroundScreening women for postnatal depression (PND) provides an opportunity to reach undetected cases and enhance pregnancy outcomes. In Zimbabwe, no validation of depression screening tools has been done on postnatal...

Role of Noncommunicable Diseases (NCDs) in Resource-Limited Settings (RLS).

As access to effective antiretroviral therapy (ART) expands globally, a decline in AIDS-related morbidity and mortality has been complicated by rising rates of noncommunicable diseases (NCDs). This review provides a brief description of NCDs and existing gaps on knowledge about NCDs among HIV-infected adults mostly in Africa. Recent reports show that one in every five persons living with HIV has a chronic illness, predominantly diabetes and/or hypertension, depression, and most of these conditions are either not diagnosed or not being managed. Human papilloma virus-associated anal dysplasia occurs among 70% of HIV-infected women in RLS. Recognizing risk factors for NCDs and providing effective screening and optimal care remains challenging. Research is urgently needed to carefully characterize HIV-associated NCDs in RLS. Such studies should provide a framework for high-priority NCDs that the limited resources can be focused on in these settings.

Detecting congenital malformations - Lessons learned from the Mpepu study, Botswana.

IntroductionA large and increasing number of HIV-infected women are conceiving on antiretroviral treatment (ART). While most antiretrovirals are considered safe in pregnancy, monitoring for rare pregnancy and infant adverse outcomes is warranted.MethodsWe conducted a retrospective secondary analysis nested within a clinical trial of infant cotrimoxazole vs. placebo prophylaxis in Botswana (the Mpepu Study). Infants were examined at birth, and at least every 3 months through 18 months of age. Abnormal physical findings and diagnostic testing revealing malformations were documented. Post hoc, a geneticist classified all reported malformations based on available documentation. Structural malformations with surgical, medical or cosmetic importance were classified as major malformations. We present a descriptive analysis of identified malformations.ResultsBetween 2011 and 2014, 2,933 HIV-infected women who enrolled in the Mpepu study delivered 2,971 live-born infants. Study staff conducted 2,944 (99%) newborn exams. One thousand eighty-eight (38%) women were taking ART at conception; 1,147 (40%) started ART during pregnancy; 442 (15%) received zidovudine monotherapy; and 223 (7%) received no antiretroviral during pregnancy. Of 33 reported anomalies, 25 (76%) met congenital malformations criteria, 10 (30%) were classified as major malformations, 4 (40%) of which were identified after the birth exam.DiscussionOur results highlight the importance of staff training on identification of congenital malformations, programmatic monitoring beyond the birth examination and the value of geneticist involvement in the malformations classification process in resource-limited settings. These elements will be important to fully define antiretroviral drug safety in pregnancy.SignificanceSurveillance systems for monitoring the safety of antiretroviral use during pregnancy among HIV-infected women in resource-limited setting are lacking. The World Health Organization’s published programmatic recommendations for such surveillance systems represents the gold standard. We employed data from a clinical trial in Botswana, a country with a generalized HIV epidemic and high antiretroviral uptake by HIV-infected women, to highlight practical opportunities to strengthen congenital malformation surveillance systems in these settings where over 1 million HIV infected pregnant women reside.Trial registrationClinical Trials.gov NCT01229761

Performance of p16INK4a ELISA as a primary cervical cancer screening test among a large cohort of HIV-infected women in western Kenya: a 2-year cross-sectional study

ObjectiveA biomarker with increased specificity for cervical dysplasia compared with human papillomavirus (HPV) testing would be an attractive option for cervical cancer screening among HIV-infected women in resource-limited settings. p16INK4a...

Maternal influenza immunisation in resource-limited settings

Pregnant women and young infants are at high risk of developing severe infl uenza. 1,2 Among infants, those younger than 6 months have the highest risk of developing complications associated with infl uenza; 3 however, antiviral treatments and infl uenza vaccines are not approved in this age group. Given that infl uenza vaccines administered to pregnant women have shown a good safety profi le 4 and effi cacy to prevent infl uenza in infants younger than 6 months, 5,6 maternal immunisation seems to be an important strategy to protect both pregnant women and their infants. WHO targets seasonal infl uenza vaccination of pregnant women as a high priority. 7 Most high-income countries recommend maternal infl uenza immunisation to reduce the burden of infl uenza in the pregnant woman and her infant. 8 However, additional data are needed to support decisions about introduction of infl uenza vaccine in pregnant women in resource-limited settings. The Bill & Melinda Gates Foundation funded three large trials in South Africa, Mali, and Nepal, with the objective of increasing the evidence base for the eff ect of maternal infl uenza immunisation. 9 In The Lancet Infectious Diseases, Milagritos D Tapias and colleagues 10 report results of the trial done in Mali—a poorly-resourced country with high infant and maternal mortality. This is the largest randomised controlled trial evaluating the effi cacy, safety, and immuno genicity of trivalent inactivated infl uenza vaccine administered to third-trimester pregnant women to prevent infl uenza in infants younger than 6 months. 4193 women were immunised: 2018 with tri valent inactivated infl uenza vaccine and 2085 with conjugate quadrivalent meningococcal vaccine. Vaccine effi cacy against fi rst-episode laboratory confi rmed infl uenza in infants (the primary outcome) was 33·1% (95% CI 3·7–53·9) in infants born to women immunised at any time prepartum (intention-to-treat analysis), and 37·3% (7·6–57·8) in those born to women vaccinated at least 14 days prepartum (per-protocol analysis). Among participating women, vaccine effi cacy was 70·3% (95% CI 42·2–85·8) overall, 76·6% (28·4–94·3) in pregnant women, and 70·1% (28·0–89·1) in the post-partum period. There was no benefi cial eff ect of the trivalent inactivated infl uenza vaccine on birthweight. The technical and logistical feasibility of implementation of a new maternal immunisation programme was also shown with a high rate of recruitment among eligible women. Evidence of the effi cacy of maternal infl uenza immunisation to prevent infl uenza in infants in low-income countries from this trial is convincing and in agreement with fi ndings from the two previously reported randomised trials from Bangladesh (63% vaccine effi cacy, 95% CI 5–85) 5 and South Africa (48·8%, 11·6–70·4).

Abstract P085: Use of Mobile Health (mHealth) Technology to Identify Targets for Improving Cardiovascular (CV) Health for Women in a Resource-limited Community: Observations From the Washington, D.C. CV Health and Needs Assessment

Introduction: Little is understood about using mHealth technology, particularly wearable devices, to assess CV health factors among women living in resource-limited communities. Hypothesis: mHealth technology could objectively identify targets to improve CV health outcomes for women living in resource-limited settings. Methods: We conducted the Washington, D.C. CV Health and Needs Assessment (NCT01927783), community-based participatory research in predominantly African American (AA), churches in city wards with lowest median household income. Participants underwent a day-long assessment to measure CV health factors [body mass index, fasting blood glucose and cholesterol, blood pressure, fruit/vegetable (F/V) intake, physical activity (PA), smoking]. Each participant was trained on using a mHealth wristband to monitor PA during a 30-day period. PA data was wirelessly uploaded to any PA-data collection hub located at the participating churches. Participants accessed their data on a secure account from a church or home computer, and investigators accessed de-identified data from a password-protected website. CV health factors were compared across weight classes. Results: Among female participants (n=78; 99% AA; mean age= 59 years), 90% had a body mass index (BMI) categorized as overweight or obese, with 30% Class-I obesity, 19% Class-II obesity, and 17% Class-III obesity [Table]. Across weight classes, PA (per mHealth wristband) decreased and self-reported sedentary time (ST) increased (p≤0.05). F/V intake was inadequate across all classes. Diastolic blood pressure (DBP) and glucose increased across weight classes (p≤0.05); however, cholesterol, glucose, and BP were near intermediate CV health goals. Conclusions: Decreased PA, increased ST, and inadequate F/V intake are potential community intervention targets for obese women in resource-limited Washington, D.C. areas. mHealth technology can assist in focusing intervention resources to improve CV health for women in resource-limited settings.

The Preterm Effect of Antiretroviral Drugs on Total Lymphocyte Cells and CD4 Cells in HIV-Infected Pregnant Women

Background: HIV infected pregnant women are placed on antiretroviral drugs for treatment and to avoid maternal to child transmission of HIV. This study was carried out to investigate the effects of the antiretroviral drugs (ARD) on CD4 and Total Lymphocyte cell count (TLC) among these women. Method: A total of 120 women participated in this study at Bori General Hospital Nigeria. Sixty (60) of them were seropositive to HIV while 60 were seronegative. Blood sample was collected from both groups of women at 2nd and 3rd trimester. The seropositve group was placed on ARD (Nevirapine, Zidovudine) after initial collection of sample at 2 nd trimester. CD4 count and TLC were estimated in these samples using Cyflow machine and manual method respectively. Result: CD4 count and TLC were significantly (p 0.05) difference. Conclusion: Reduction of CD4 cell count and TLC at 2nd trimester in HIV- infected pregnant women showed that HIV infection depleted these immunologic markers in pregnancy. The administration of ARD from second trimester boosted the CD4 cell count and TLC among these infected pregnant women before delivery. Progressive increase in TLC alongside CD4 cell count among the women on ARD suggests that TLC could be used as a surrogate to monitor progress of treatment among HIV-infected pregnant women in resource limited settings.

Moving targets: The challenges of studying infectious diseases among pregnant women in resource limited settings

Conducting clinical trials to prevent and treat infectious diseases in pregnancy is essential to saving maternal and newborn lives, though it is fraught with challenges. We have been conducting research in malaria treatment and prevention in children and pregnant women in Blantyre, Malawi for over a decade. Here, we review some of the unique challenges that we have faced in leading research studies that with rigor and integrity and maintaining the highest ethical standard. We conclude with concrete strategies to overcome some of the apparent obstacles that frequently focus on building trust through bidirectional communication with local health workers and communities. We also highlight the key role of local and international investigators to advocate for the health of the communities in which they work.

Breast Milk of HIV-Positive Mothers Has Potent and Species-Specific In Vivo HIV-Inhibitory Activity.

Despite the nutritional and health benefits of breast milk, breast milk can serve as a vector for mother-to-child HIV transmission. Most HIV-infected infants acquire HIV through breastfeeding. Paradoxically, most infants breastfed by HIV-positive women do not become infected. This is potentially attributed to anti-HIV factors in breast milk. Breast milk of HIV-negative women can inhibit HIV infection. However, the HIV-inhibitory activity of breast milk from HIV-positive mothers has not been evaluated. In addition, while significant differences in breast milk composition between transmitting and nontransmitting HIV-positive mothers have been correlated with transmission risk, the HIV-inhibitory activity of their breast milk has not been compared. This knowledge may significantly impact the design of prevention approaches in resource-limited settings that do not deny infants of HIV-positive women the health benefits of breast milk. Here, we utilized bone marrow/liver/thymus humanized mice to evaluate the in vivo HIV-inhibitory activity of breast milk obtained from HIV-positive transmitting and nontransmitting mothers. We also assessed the species specificity and biochemical characteristics of milk's in vivo HIV-inhibitory activity and its ability to inhibit other modes of HIV infection. Our results demonstrate that breast milk of HIV-positive mothers has potent HIV-inhibitory activity and indicate that breast milk can prevent multiple routes of infection. Most importantly, this activity is unique to human milk. Our results also suggest multiple factors in breast milk may contribute to its HIV-inhibitory activity. Collectively, our results support current recommendations that HIV-positive mothers in resource-limited settings exclusively breastfeed in combination with antiretroviral therapy. Approximately 240,000 children become infected with HIV annually, the majority via breastfeeding. Despite daily exposure to virus in breast milk, most infants breastfed by HIV-positive women do not acquire HIV. The low risk of breastfeeding-associated HIV transmission is likely due to antiviral factors in breast milk. It is well documented that breast milk of HIV-negative women can inhibit HIV infection. Here, we demonstrate, for the first time, that breast milk of HIV-positive mothers (nontransmitters and transmitters) inhibits HIV transmission. We also demonstrate that breast milk can prevent multiple routes of HIV acquisition and that this activity is unique to human milk. Collectively, our results support current guidelines which recommend that HIV-positive women in resource-limited settings exclusively breastfeed in combination with infant or maternal antiretroviral therapy.

English

Cervical cancer is the fourth most common cancer in women worldwide, and the most common cancer in women in resource limited settings. Regardless of the stage at which a diagnosis of cancer is made, individuals who receive such a diagnosis are stressed both psychologically and emotionally, thus they need to employee certain mechanism in order to cope. Using Lazarus and Folkman’s Transaction Model of Stress and Coping, a qualitative descriptive phenomenological research was conducted to explore how patients react to a diagnosis of cervical cancer, and the coping strategies they utilize in order to adapt. A total of 19 cervical cancer patients were interviewed who had lived with cancer for three months and above. Data were analyzed using content analysis. Three main characteristic reactions/feelings at the time of diagnosis were identified including; fear of eminent death, self-pity, and disbelief. Fear of eminent death was the most profound. Meanwhile five themes emerged on how the patients were coping with their diagnosis; faith in God coupled with prayer, support from family, support from Church, support from medical personnel, and assurance from fellow patients and cancer survivors. In conclusion it was acknowledged that a diagnosis of cervical cancer is a stressful to those affected as evidenced by negative reactions from those who receive such diagnosis is stressful. Therefore, individuals who are diagnoses with cervical cancer irrespective of the stage, ought to employee certain coping mechanisms in order to adapt.   Key words: Stress, coping mechanisms, cervical cancer patients, adaptation.