Uptake and safety of community-based "screen-and-treat" with thermal ablation preventive therapy for cervical cancer prevention in rural Lilongwe, Malawi.

Malawi has the highest invasive cervical cancer (ICC) mortality rate worldwide, and ICC is the leading cause of cancer death among women. In 2004, Malawi adopted visual inspection with acetic acid (VIA) and ablative treatment with cryotherapy. However, screening coverage has remained low (<30%) and few women (<50%) who require ablative treatment receive it. Additional barriers include long distances to health facilities and challenges with maintaining gas supplies. Thermal ablation is a safe and effective alternative to cryotherapy. We assessed the safety and uptake of community-based ICC screening with VIA and same-day treatment using a handheld thermocoagulator (HTU) in rural Malawi. We held educational talks alongside community leaders and conducted VIA screening in nonclinic community settings to nonpregnant women aged 25 to 49 years without history of hysterectomy or genital cancer/precancer. Eligible women received same-day thermal ablation and HIV testing/counseling. We collected cervical biopsies before treatment and followed up women at Weeks 6 and 12, with repeat biopsy at Week 12. Between July and August 2017, 408 (88%) of 463 eligible women underwent VIA. Overall, 7% (n = 30) of women had a positive VIA, of whom 93% (n = 28) underwent same-day thermal ablation. Among the 30 VIA-positive women, 5 had cervical intraepithelial neoplasia (CIN) 1, 4 had CIN 2/3 and 21 had benign histologic findings. Abnormal vaginal discharge (60%) and light vaginal bleeding (52%) were the most reported adverse events. There was high uptake of the community-based ICC screening in the study population and treatment was safe in this setting. Similar strategies that minimize false-positive results are urgently needed in Malawi.

Syndromes Associated with Sexually Transmitted Infections in Lilongwe, Malawi: Burden and Trends, 2006 to 2015.

ABSTRACT: Monitoring the burden of and trends in sexually transmitted infection syndromes is useful in informing syndromic management guidelines. Among sexually transmitted infection clinic patients in Lilongwe, Malawi, between 2006 and 2015, genital discharge, lower abdominal pain, and genital ulcer syndromes were common. Prevalence of most syndromes remained stable during the 10-year period.

Women's experiences in a community-based screen-and-treat cervical cancer prevention program in rural Malawi: a qualitative study.

BACKGROUND: Malawi has the world's highest cervical cancer incidence and mortality due to high rate of HIV coupled with inadequate screening and treatment services. The country's cervical cancer control program uses visual inspection with acetic acid (VIA) and cryotherapy, but screening is largely limited by poor access to facilities, high cost of cryotherapy gas, and high loss-to-follow-up. To overcome these limitations, we implemented a community-based screen-and-treat pilot program with VIA and thermocoagulation. Through a qualitative study, we explore the experiences of women who underwent this community-based pilot screening program. METHODS: We implemented our pilot program in rural Malawi and conducted an exploratory qualitative sub-study. We conducted in-depth interviews with women who were treated with thermocoagulation during the program. We used semi-structured interviews to explore screen-and-treat experience, acceptability of the program and attitudes towards self-sampling for HPV testing as an alternative screening method. Content analysis was conducted using NVIVO v12. RESULTS: Between July - August 2017, 408 participants eligible for screening underwent VIA screening. Thirty participants had VIA positive results, of whom 28 underwent same day thermocoagulation. We interviewed 17 of the 28 women who received thermocoagulation. Thematic saturation was reached at 17 interviews. All participants reported an overall positive experience with the community-based screen-and-treat program. Common themes were appreciation for bringing screening directly to their villages, surprise at the lack of discomfort, and the benefits of access to same day treatment immediately following abnormal screening. Negative experiences were rare and included discomfort during speculum exam, long duration of screening and challenges with complying with postprocedural abstinence. Most participants felt that utilizing self-collected HPV testing could be acceptable for screening in their community. CONCLUSIONS: Our exploratory qualitative sub-study demonstrated that the community-based screen-and-treat with VIA and thermocoagulation was widely accepted. Participants valued the accessible, timely, and painless thermocoagulation treatment and reported minimal side effects. Future considerations for reaching rural women can include community-based follow-up, cervical cancer education for male partners and self-sampling for HPV testing.

Recruiting the social contacts of patients with STI for HIV screening in Lilongwe, Malawi: process evaluation and assessment of acceptability.

OBJECTIVES: To explore acceptability of recruiting social contacts for HIV and sexually transmitted infection (STI) screening in Lilongwe, Malawi. METHODS: In this observational study, three groups of 'seed' patients were enrolled: 45 HIV-infected patients with STI, 45 HIV-uninfected patients with STI and 45 community controls, who were also tested for HIV as part of the study. Each seed was given five coupons and asked to recruit up to five social contacts to the STI clinic. Seeds were told the programme for contacts would include HIV testing, STI screening and general health promotion. Seeds were asked to return after 1 month to report on the contact recruitment process. Seeds received $2 for each successfully recruited contact. RESULTS: Eighty-nine seeds (66%) returned for 1-month follow-up with no difference between the three seed groups (p=0.9). Returning seeds reported distributing most of their coupons (mean=4.1) and discussing each feature of the programme with most contacts-HIV testing (90%), STI screening (87%) and health promotion (91%). Seeds reported discussing their own HIV status with most contacts (52%), with a lower proportion of HIV-infected seeds discussing their HIV status (22%) than HIV-uninfected seeds (81%) or community seeds (64%) (p<0.001). Contact recruitment did not vary with socioeconomic status. CONCLUSIONS: Most seeds distributed all coupons and reported describing all aspects of the programme to most contacts. Patients with STI are able to act as health promoters within their social networks and may be a critical link to increasing STI and HIV status awareness among high-risk groups.

Comparison of viral Env proteins from acute and chronic infections with subtype C human immunodeficiency virus type 1 identifies differences in glycosylation and CCR5 utilization and suggests a new strategy for immunogen design.

Understanding human immunodeficiency virus type 1 (HIV-1) transmission is central to developing effective prevention strategies, including a vaccine. We compared phenotypic and genetic variation in HIV-1 env genes from subjects in acute/early infection and subjects with chronic infections in the context of subtype C heterosexual transmission. We found that the transmitted viruses all used CCR5 and required high levels of CD4 to infect target cells, suggesting selection for replication in T cells and not macrophages after transmission. In addition, the transmitted viruses were more likely to use a maraviroc-sensitive conformation of CCR5, perhaps identifying a feature of the target T cell. We confirmed an earlier observation that the transmitted viruses were, on average, modestly underglycosylated relative to the viruses from chronically infected subjects. This difference was most pronounced in comparing the viruses in acutely infected men to those in chronically infected women. These features of the transmitted virus point to selective pressures during the transmission event. We did not observe a consistent difference either in heterologous neutralization sensitivity or in sensitivity to soluble CD4 between the two groups, suggesting similar conformations between viruses from acute and chronic infection. However, the presence or absence of glycosylation sites had differential effects on neutralization sensitivity for different antibodies. We suggest that the occasional absence of glycosylation sites encoded in the conserved regions of env, further reduced in transmitted viruses, could expose specific surface structures on the protein as antibody targets.

Predicting partner HIV testing and counseling following a partner notification intervention.

Provider-assisted methods of partner notification increase testing and counseling among sexual partners of patients diagnosed with HIV, however they are resource-intensive. The sexual partners of individuals enrolled in a clinical trial comparing different methods of HIV partner notification were analyzed to identify who was unlikely to seek testing on their own. Unconditional logistic regression was used to identify partnership characteristics, which were assigned a score based on their coefficient in the final model, and a risk score was calculated for each participant. The risk score included male partner sex, relationship duration 6-24 months, and index education > primary. A risk score of ≥ 2 had a sensitivity of 68% and specificity of 78% in identifying partners unlikely to seek testing on their own. A risk score to target partner notification can reduce the resources required to locate all partners in the community while increasing the testing yield compared to patient-referral.

Perceptions of cervical cancer and motivation for screening among women in Rural Lilongwe, Malawi: A qualitative study.

INTRODUCTION: Cervical cancer is the leading cause of cancer death among women in Malawi. Low awareness of cervical cancer and negative perceptions of screening can prevent women from participating in preventative strategies. We sought to explore perceptions and motivations for screening among women who participated in a cervical cancer screen-and-treat pilot study in rural Malawi. MATERIALS AND METHODS: We conducted a qualitative sub-study of a community-based cervical cancer screen-and-treat pilot study in rural Lilongwe between July-August 2017. From October 2017-February 2018, 17 women who underwent screening using visual inspection with acetic acid (VIA) and same-day thermal ablation treatment were recruited at their 12-week follow-up visit post treatment to participate in this qualitative sub-study. Semi-structured interview guides that explored baseline knowledge of cervical cancer, perceptions, and motivation for screening were used for in-depth interviews (IDIs). IDIs were conducted in the local language, Chichewa, translated and transcribed to English. Data was analyzed using NVivo® V12.0. RESULTS: Findings included fatalistic views on cancer, but limited knowledge specific to cervical cancer. Misconceptions of cervical cancer screening were common; however, there was a unique understanding of screening as prevention (i.e., finding and treating early disease to prevent progression to worsening disease). This understanding appeared to stem from HIV prevention concepts known to the community. Motivations for screening included desire to know one's health status, convenience of community-based screening, and peer encouragement. CONCLUSION: Despite limited knowledge of cervical cancer and misconceptions of screening, the concept of screening for prevention, desire to know one's health status, convenient access, and peers' influence were motivators for participation in screening. Cervical cancer screen-and-treat programs in high HIV prevalence areas should consider utilizing language that parallels HIV prevention language to communicate the need for cervical cancer screening and treatment and utilize prevention concepts that may already be familiar to women living there.

RTS,S vaccination is associated with reduced parasitemia and anemia among children diagnosed with malaria in the outpatient department of a district hospital in rural Malawi.

The RTS,S/AS01 malaria vaccine was recently approved by the World Health Organization, but real-world effectiveness is still being evaluated. We measured hemoglobin concentration and parasite density in vaccinated and unvaccinated children who had been diagnosed with malaria by rapid diagnostic test (mRDT) in the outpatient department of a rural hospital in Malawi. Considering all mRDT positive participants, the mean hemoglobin concentration among unvaccinated participants was 9.58 g/dL. There was improvement to 9.82 g/dL and 10.36 g/dL in the 1 or 2 dose group (p = 0.6) and the 3 or 4 dose group (p = 0.0007), respectively. Among a microscopy positive subset of participants, mean hemoglobin concentration of unvaccinated participants was 9.55 g/dL with improvement to 9.82 g/dL in the 1 or 2 dose group (p = 0.6) and 10.41 g/dL in the 3 or 4 dose group (p = 0.003). Mean parasite density also decreased from 115,154 parasites/µL in unvaccinated children to 87,754 parasites/µL in children who had received at least one dose of RTS,S (p = 0.04). In this study population, vaccination was associated with significant improvements in both hemoglobin concentration and parasite density in the setting of real-world administration of the RTS,S/AS01 vaccine.

Lessons learned from a rural, community-based cervical cancer screen-and-treat pilot study in Malawi.

Objectives: Invasive cervical cancer (ICC) is the leading cause of cancer-related death among women in Malawi. Barriers to screening for ICC in Malawi, such as long distances to health facilities and lack of public education about ICC, have hindered participation of women in ICC prevention programs. Given the burden of disease and barriers to screening, we implemented a community-based ICC screen-and-treat pilot study and present its successes and challenges. Study design: This study was a screen-and-treat pilot study using Visual Inspection with Acetic acid (VIA) for screening and same-day thermal ablation for treatment of pre-cancerous lesions. The pilot was implemented in four rural community settings in Lilongwe District, Malawi. Methods: With consultation from local leaders, as well as the UNC Project-Malawi Community Department and the Community Advisory Board, a team of researchers designed a rural, community-based ICC screen-and-treat pilot study. Over a 5-week period, we travelled to four rural communities to provide information about and screening for ICC and HIV through our study. The four selected rural locations were about an hour drive from Lilongwe City, Malawi. Detailed field notes were taken by study staff and then later analyzed and categorized as either strengths or challenges. Results: Successes included support from local leaders, high uptake of screening (408 women underwent VIA, representing 88% of eligible women), positive experiences during screening, and good communication between study staff and participants. This communication enabled us to quickly address misperceptions about the study intent and procedures and to better understand some of the barriers to care. Challenges included insufficient medication for diagnosed sexually transmitted infections, finding ways to engage interested women who were ineligible due to young age, and not screening interested women because they needed male partner approval. Conclusion: Community-based screen-and-treat programs with thermal ablation for ICC can be an effective way to engage hard-to-reach women in ICC preventive care. Our findings support existing literature which suggests that involvement of local leadership, women from the community, and their male partners, as well as ongoing peer education, may facilitate greater participation in ICC screening and treatment. In addition, we found ongoing communication between study staff and participants to be mutually beneficial. Finally, we suggest that future interventions consider bundling sexually transmitted infection treatment into ICC preventive care when engaging hard-to-reach populations.

Barriers to follow-up after an abnormal cervical cancer screening result and the role of male partners: a qualitative study.

INTRODUCTION: Cervical cancer is the leading cause of cancer deaths among women in Malawi, but preventable through screening. Malawi primarily uses visual inspection with acetic acid (VIA) for screening, however, a follow-up for positive screening results remains a major barrier, in rural areas. We interviewed women who underwent a community-based screen-and-treat campaign that offered same-day treatment with thermocoagulation, a heat-based ablative procedure for VIA-positive lesions, to understand the barriers in accessing post-treatment follow-up and the role of male partners in contributing to, or overcoming these barriers. METHODS: We conducted in-depths interviews with 17 women recruited in a pilot study that evaluated the safety and acceptability of community-based screen-and-treat programme using VIA and thermocoagulation for cervical cancer prevention in rural Lilongwe, Malawi. Ten of the women interviewed presented for post-treatment follow-up at the healthcare facility and seven did not. The interviews were analysed for thematic content surrounding barriers for attending for follow-up and role of male partners in screening. RESULTS: Transportation was identified as a major barrier to post-thermocoagulation follow-up appointment, given long distances to the healthcare facility. Male partners were perceived as both a barrier for some, that is, not supportive of 6-week post-thermocoagulation abstinence recommendation, and as an important source of support for others, that is, encouraging follow-up attendance, providing emotional support to maintaining post-treatment abstinence and as a resource in overcoming transportation barriers. Regardless, the majority of women desired more male partner involvement in cervical cancer screening. CONCLUSION: Despite access to same-day treatment, long travel distances to health facilities for post-treatment follow-up visits remained a major barrier for women in rural Lilongwe. Male partners were identified both as a barrier to, and an important source of support for accessing and completing the screen-and-treat programme. To successfully eliminate cervical cancer in Malawi, it is imperative to understand the day-to-day barriers women face in accessing preventative care.

Amplified transmission of HIV-1: comparison of HIV-1 concentrations in semen and blood during acute and chronic infection.

OBJECTIVES: This study was conducted to compare viral dynamics in blood and semen between subjects with antibody negative, acute HIV-1 infection and other subjects with later stages of infection. DESIGN: A prospective cohort study was embedded within a cross-sectional study of HIV screening in a Lilongwe, Malawi STD clinic. METHODS: Blood samples from HIV antibody negative or indeterminate volunteers were used to detect HIV RNA in plasma using a pooling strategy. Blood and seminal plasma HIV-1 RNA concentrations were measured over 16 weeks. RESULTS: Sixteen men with acute HIV infection and 25 men with chronic HIV infection were studied. Blood viral load in subjects with acute HIV infection was highest about 17 days after infection (mean +/- SE, 6.9 +/- 0.5 log10 copies/ml), while semen viral load peaked about 30 days after infection (4.5 +/- 0.4 log10 copies/ml). Semen viral load declined by 1.7 log10 to a nadir by week 10 of HIV infection. Semen and blood viral loads were more stable in chronically infected subjects over 16 weeks. Higher semen levels of HIV RNA were noted in subjects with low CD4 cell counts. CONCLUSIONS: These results provide a biological explanation for reported increases in HIV transmission during the very early (acute) and late stages of infection. Recognizing temporal differences in HIV shedding in the genital tract is important in the development of effective HIV prevention strategies.

Improved detection of acute HIV-1 infection in sub-Saharan Africa: development of a risk score algorithm.

OBJECTIVE: Individuals with acute (preseroconversion) HIV infection (AHI) are important in the spread of HIV. The identification of AHI requires the detection of viral proteins or nucleic acids with techniques that are often unaffordable for routine use. To facilitate the efficient use of these tests, we sought to develop a risk score algorithm for identifying likely AHI cases and targeting the tests towards those individuals. DESIGN: A cross-sectional study of 1448 adults attending a sexually transmitted infections (STI) clinic in Malawi. METHODS: Using logistic regression, we identified risk behaviors, symptoms, HIV rapid test results, and STI syndromes that were predictive of AHI. We assigned a model-based score to each predictor and calculated a risk score for each participant. RESULTS: Twenty-one participants (1.45%) had AHI, 588 had established HIV infection, and 839 were HIV-negative. AHI was strongly associated with discordant rapid HIV tests and genital ulcer disease (GUD). The algorithm also included diarrhea, more than one sexual partner in 2 months, body ache, and fever. Corresponding predictor scores were 1 for fever, body ache, and more than one partner; 2 for diarrhea and GUD; and 4 for discordant rapid tests. A risk score of 2 or greater was 95.2% sensitive and 60.5% specific in detecting AHI. CONCLUSION: Using this algorithm, we could identify 95% of AHI cases by performing nucleic acid or protein tests in only 40% of patients. Risk score algorithms could enable rapid, reliable AHI detection in resource-limited settings.

Targeted screening of at-risk adults for acute HIV-1 infection in sub-Saharan Africa.

BACKGROUND: Patients with acute HIV-1 infection (AHI) have elevated infectivity, but cannot be diagnosed using antibody-based testing. Approaches to screen patients for AHI are urgently needed to enable counselling and treatment to reduce onward transmission. METHODS: We pooled data from four African studies of high-risk adults that evaluated symptoms and signs compatible with acute retroviral syndrome and tested for HIV-1 at each visit. AHI was defined as detectable plasma viral load or p24 antigen in an HIV-1-antibody-negative patient who subsequently seroconverted. Using generalized estimating equation, we identified symptoms, signs, and demographic factors predictive of AHI, adjusting for study site. We assigned a predictor score to each statistically significant predictor based on its beta coefficient, summing predictor scores to calculate a risk score for each participant. We evaluated the performance of this algorithm overall and at each site. RESULTS: We compared 122 AHI visits with 45 961 visits by uninfected patients. Younger age (18-29 years), fever, fatigue, body pains, diarrhoea, sore throat, and genital ulcer disease were independent predictors of AHI. The overall area under the receiver operating characteristics curve (AUC) for the algorithm was 0.78, with site-specific AUCs ranging from 0.61 to 0.89. A risk score of at least 2 would indicate AHI testing for 5-50% of participants, substantially decreasing the number needing testing. CONCLUSION: Our targeted risk score algorithm based on seven characteristics reduced the number of patients needing AHI testing and had good performance overall. We recommend this risk score algorithm for use by HIV programs in sub-Saharan Africa with capacity to test high-risk patients for AHI.

STI patients are effective recruiters of undiagnosed cases of HIV: results of a social contact recruitment study in Malawi.

BACKGROUND: Patients with newly diagnosed HIV may be part of social networks with elevated prevalence of undiagnosed HIV infection. Social network recruitment by persons with newly diagnosed HIV may efficiently identify undiagnosed cases of HIV infection. We assessed social network recruitment as a strategy for identifying undiagnosed cases of HIV infection. METHODS: In a sexually transmitted infection (STI) clinic in Lilongwe, Malawi, 3 groups of 45 "seeds" were enrolled: STI patients with newly diagnosed HIV, STI patients who were HIV-uninfected, and community controls. Seeds were asked to recruit up to 5 social "contacts" (sexual or nonsexual). Mean number of contacts recruited per group was calculated. HIV prevalence ratios (PRs) and number of contacts needed to test to identify 1 new case of HIV were compared between groups using generalized estimating equations with exchangeable correlation matrices. RESULTS: Mean number of contacts recruited was 1.3 for HIV-infected clinic seeds, 1.8 for HIV-uninfected clinic seeds, and 2.3 for community seeds. Contacts of HIV-infected clinic seeds had a higher HIV prevalence (PR: 3.2, 95% confidence interval: 1.3 to 7.8) than contacts of community seeds, but contacts of HIV-uninfected clinic seeds did not (PR: 1.1, 95% confidence interval: 0.4 to 3.3). Results were similar when restricted to nonsexual contacts. To identify 1 new case of HIV, it was necessary to test 8 contacts of HIV-infected clinic seeds, 10 contacts of HIV-uninfected clinic seeds, and 18 contacts of community seeds. CONCLUSIONS: Social contact recruitment by newly diagnosed STI patients efficiently led to new HIV diagnoses. Research to replicate findings and guide implementation is needed.

HIV partner notification is effective and feasible in sub-Saharan Africa: opportunities for HIV treatment and prevention.

BACKGROUND: Sexual partners of persons with newly diagnosed HIV infection require HIV counseling, testing and, if necessary, evaluation for therapy. However, many African countries do not have a standardized protocol for partner notification, and the effectiveness of partner notification has not been evaluated in developing countries . METHODS: Individuals with newly diagnosed HIV infection presenting to sexually transmitted infection clinics in Lilongwe, Malawi, were randomized to 1 of 3 methods of partner notification: passive referral, contract referral, or provider referral. The passive referral group was responsible for notifying their partners themselves. The contract referral group was given seven days to notify their partners, after which a health care provider contacted partners who had not reported for counseling and testing. In the provider referral group, a health care provider notified partners directly. RESULTS: Two hundred forty-five index patients named 302 sexual partners and provided locator information for 252. Among locatable partners, 107 returned for HIV counseling and testing; 20 of 82 [24%; 95% confidence interval (CI): 15% to 34%] partners returned in the passive referral arm, 45 of 88 (51%; 95% CI: 41% to 62%) in the contract referral arm, and 42 of 82 (51%; 95% CI: 40% to 62%) in the provider referral arm (P < 0.001). Among returning partners (n = 107), 67 (64%) of were HIV infected with 54 (81%) newly diagnosed. DISCUSSION: This study provides the first evidence of the effectiveness of partner notification in sub-Saharan Africa. Active partner notification was feasible, acceptable, and effective among sexually transmitted infections clinic patients. Partner notification will increase early referral to care and facilitate risk reduction among high-risk uninfected partners.

Rapid, real-time detection of acute HIV infection in patients in Africa.

BACKGROUND: We conducted a prospective study to evaluate methods of detecting clients with sexually transmitted diseases (STDs) who were acutely coinfected with human immunodeficiency virus (HIV) in Lilongwe, Malawi. METHODS: After informed consent was obtained, all clients with acute STDs were offered voluntary HIV counseling and testing by 2 rapid antibody tests. Samples from rapid test-negative or -discordant subjects were pooled (50 : 5 : 1) and tested for HIV RNA. Western blots were performed on all rapid test-discordant specimens with detectable HIV RNA. A subset of specimens received p24 antigen testing with standard and/or ultrasensitive methods. Patients with possible acute HIV infection were followed to confirm seroconversion. RESULTS: A total of 1450 clients (34% female and 66% male) agreed to testing, of whom 588 (40.55%) had established HIV infection and 21 (1.45%) had acute infection. Discordant rapid antibody tests identified 7 of 21 (33.3% sensitivity), standard p24 antigen identified 12 of 16 (75% sensitivity), and ultrasensitive p24 antigen identified 15 of 17 (88% sensitivity) acute cases. By definition, the sensitivity of the RNA assay was 100%. CONCLUSIONS: Real-time pooled RNA testing for the detection of acute HIV infection is feasible in resource-limited settings. However, parallel rapid testing and p24 antigen testing are technologically simpler and together may detect approximately 90% of acute cases.