Female genital schistosomiasis burden and risk factors in two endemic areas in Malawi nested in the Morbidity Operational Research for Bilharziasis Implementation Decisions (MORBID) cross-sectional study.

BACKGROUND: Female genital schistosomiasis (FGS), caused by the parasite Schistosoma haematobium (Sh), is prevalent in Sub-Saharan Africa. FGS is associated with sexual dysfunction and reproductive morbidity, and increased prevalence of HIV and cervical precancerous lesions. Lack of approved guidelines for FGS screening and diagnosis hinder accurate disease burden estimation. This study evaluated FGS burden in two Sh-endemic areas in Southern Malawi by visual and molecular diagnostic methods. METHODOLOGY/PRINCIPAL FINDINGS: Women aged 15-65, sexually active, not menstruating, or pregnant, were enrolled from the MORBID study. A midwife completed a questionnaire, obtained cervicovaginal swab and lavage, and assessed FGS-associated genital lesions using hand-held colposcopy. 'Visual-FGS' was defined as specific genital lesions. 'Molecular-FGS' was defined as Sh DNA detected by real-time PCR from swabs. Microscopy detected urinary Sh egg-patent infection. In total, 950 women completed the questionnaire (median age 27, [IQR] 20-38). Visual-and molecular-FGS prevalence were 26·9% (260/967) and 8·2% (78/942), respectively. 6·5% of women with available genital and urinary samples (38/584) had egg-patent Sh infection. There was a positive significant association between molecular- and visual-FGS (AOR = 2·9, 95%CI 1·7-5·0). 'Molecular-FGS' was associated with egg-patent Sh infection (AOR = 7·5, 95% CI 3·27-17·2). Some villages had high 'molecular-FGS' prevalence, despite <10% prevalence of urinary Sh among school-age children. CONCLUSIONS/SIGNIFICANCE: Southern Malawi carries an under-recognized FGS burden. FGS was detectable in villages not eligible for schistosomiasis control strategies, potentially leaving girls and women untreated under current WHO guidelines. Validated field-deployable methods could be considered for new control strategies.

Elimination of lymphatic filariasis as a public health problem in Malawi.

BACKGROUND: Lymphatic filariasis (LF) is a parasitic disease transmitted by mosquitoes, causing severe pain, disfiguring, and disabling clinical conditions such as lymphoedema and hydrocoele. LF is a global public health problem affecting 72 countries, primarily in Africa and Asia. Since 2000, the World Health Organization (WHO) has led the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to support all endemic regions. This paper focuses on the achievements of the Malawi LF Elimination Programme between 2000 and 2020 to eliminate LF as a public health problem, making it the second sub-Saharan country to receive validation from the WHO. METHODOLOGY/PRINCIPAL FINDINGS: The Malawi LF Programme addressed the widespread prevalence of LF infection and disease across the country, using the recommended WHO GPELF strategies and operational research initiatives in collaboration with key national and international partners. First, to stop the spread of infection (i.e., interrupt transmission) and reduce the circulating filarial antigen prevalence from as high as 74.4% to below the critical threshold of 1-2% prevalence, mass drug administration (MDA) using a two-drug regime was implemented at high coverage rates (>65%) of the total population, with supplementary interventions from other programmes (e.g., malaria vector control). The decline in prevalence was monitored and confirmed over time using several impact assessment and post-treatment surveillance tools including the standard sentinel site, spot check, and transmission assessment surveys and alternative integrated, hotspot, and easy-access group surveys. Second, to alleviate suffering of the affected populations (i.e., control morbidity) the morbidity management and disability prevention (MMDP) package of care was implemented. Specifically, clinical case estimates were obtained via house-to-house patient searching activities; health personnel and patients were trained in self-care protocols for lymphoedema and/or referrals to hospitals for hydrocoele surgery; and the readiness and quality of treatment and services were assessed with new survey tools. CONCLUSIONS: Malawi's elimination of LF will ensure that future generations are not infected and suffer from the disfiguring and disabling disease. However, it will be critical that the Malawi LF Elimination programme remains vigilant, focussing on post-elimination surveillance and MMDP implementation and integration into routine health systems to support long-term sustainability and ongoing success. SUMMARY: Lymphatic filariasis, also known as elephantiasis, is a disabling, disfiguring, and painful disease caused by a parasite that infected mosquitoes transmit to millions of people worldwide. Since 2000, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) has supported endemic countries such as Malawi in south-eastern Africa, to eliminate the disease as a public health problem. The Malawi National LF Elimination Programme has worked tirelessly over the past two decades to implement the GPELF recommended strategies to interrupt the transmission with a two-drug regime, and to alleviate suffering in patients with lymphoedema and/or hydrocoele through morbidity management and disability prevention. Additionally, the LF Programme has collaborated with national and international stakeholders to implement a range of supplementary operational research projects to address outstanding knowledge gaps and programmatic barriers. In 2020, the World Health Organisation validated that Malawi had successfully eliminated LF as a public health problem, making it the second country in sub-Saharan Africa to achieve this, which is remarkable given that Malawi previously had very high infection rates. The LF Programme now remains vigilant, putting its efforts towards post-elimination surveillance and the continued implementation of care for patients with chronic conditions. Malawi's elimination of LF will ensure that future generations are not affected by this devastating disease.

Acceptability and feasibility of tuberculosis and diabetes mellitus bidirectional screening and joint treatment services in Malawi: a cross-sectional study and a policy document review.

OBJECTIVES: A cross-sectional and a policy document review study was performed to investigate perceived acceptability and feasibility to implementing different integration measures for tuberculosis (TB) and diabetes mellitus (DM) healthcare among healthcare workers (HCWs) and health managers, and to describe policy influence through a policy documents review in Malawi. SETTING: The survey was performed at eight hospitals, ministry of health offices and 10 non-governmental organisations. We collected data in March and April 2021. PARTICIPANTS: Of 95 HCWs and health managers invited; 92 participated. 21/92 (23%) were female, and 17/92 (18%) participants were from clinics that piloted the integrated care for TB and DM. OUTCOME MEASURES: We described awareness levels on TB/DM comorbidity, perceptions and experiences in TB/DM care. Furthermore, development processes and contents of included documents were analysed. RESULTS: 16/17 (94%) of HCWs from clinics piloting integrated care and 65/75 (86%) HCWs from hospitals that do not use integrated care for TB and DM responded that integrated care was acceptable and feasible. In qualitative data, shortage of resources, inadequate information sharing were common themes. We included seven relevant documents for the analysis. On development process and content, six of seven documents were scored ≥70%. In these documents, DM is a recognised risk factor for TB, and integration of healthcare services for infectious diseases and non-communicable diseases is recommended, however, these documents lacked information specifically on integrated care for TB and DM. CONCLUSION: In this study, we identified inadequate information sharing, and lack of resources as major factors impeding implementation of integration of services, however, awareness on TB/DM comorbidity was high.

Bidirectional screening and treatment outcomes of diabetes mellitus (DM) and Tuberculosis (TB) patients in hospitals with measures to integrate care of DM and TB and those without integration measures in Malawi.

INTRODUCTION: There are efforts in low and middle-income countries (LMICs) to integrate Tuberculosis (TB) and Diabetes mellitus (DM) healthcare services, as encouraged by WHO and other international health organizations. However, evidence on actual effect of different integration measures on bidirectional screening coverages and or treatment outcomes for both diseases in LMICs is scarce. OBJECTIVES AND METHODS: Retrospective chart review analysis was conducted to determine effects of integrated care on bidirectional screening and treatment outcomes for both TB patients and people with DM (PWD) recruited in eight Malawian hospitals. Data of ≥ 15 years old patients registered between 2016 to August 2019 were collected and analysed. RESULTS: 557 PWDs (mean age 54) and 987 TB patients (mean age 41) were recruited. 64/557 (11.5%) PWDs and 105/987 (10.6%) of TB patients were from an integrating hospital. 36/64 (56.3%) PWDs were screened for TB in integrated healthcare as compared to 5/493 (1.0%) in non-integrated care; Risk Difference (RD) 55.2%, (95%CI 43.0, 67.4), P < 0.001, while 10/105 (9.5%) TB patients were screened for DM in integrated healthcare as compared to 43/882 (4.9%) in non-integrated care; RD 4.6%, (95%CI - 1.1, 10.4), P = 0.065. Of the PWDs screened, 5/41 (12.2%) were diagnosed with TB, while 5/53 (9.4%) TB patients were diagnosed with DM. On TB treatment outcomes, 71/508 (14.8%) were lost to follow up in non-integrated care and none in integrated care were lost to follow-up; RD - 14.0%, (95%CI: - 17.0,-11.0), p < 0.001. Among PWDs, 40/493 (8.1%) in non-integrated care and 2/64 (3.1%) were lost to follow up in integrated care; RD - 5.0%, (95%CI:-10.0, - 0.0); P = 0.046. After ≥ 2 years of follow up, 62.5% PWDs in integrated and 41.8% PWDs in non-integrated care were retained in care, RD 20.7, (95%CI: 8.1, 33.4), P = 0.001. CONCLUSION: We found higher bidirectional screening coverage and less loss to follow-up in one centre that made more efforts to implement integrated measures for TB and DM care than in 7 others that did not make these efforts. Decisions on local programs to integrate TB/DM care should be taken considering currently rather weak evidence and barriers faced in the local context as well as existing guidelines.

Prevention of cervical cancer through two HPV-based screen-and-treat implementation models in Malawi: protocol for a cluster randomized feasibility trial.

BACKGROUND: Cervical cancer is the leading cause of cancer incidence and mortality among Malawian women, despite being a largely preventable disease. Implementing a cervical cancer screening and preventive treatment (CCSPT) program that utilizes rapid human papillomavirus (HPV) testing on self-collected cervicovaginal samples for screening and thermal ablation for treatment may achieve greater coverage than current programs that use visual inspection with acetic acid (VIA) for screening and cryotherapy for treatment. Furthermore, self-sampling creates the opportunity for community-based screening to increase uptake in populations with low screening rates. Malawi's public health system utilizes regularly scheduled outreach and village-based clinics to provide routine health services like family planning. Cancer screening is not yet included in these community services. Incorporating self-sampled HPV testing into national policy could address cervical cancer screening barriers in Malawi, though at present the effectiveness, acceptability, appropriateness, feasibility, and cost-effectiveness still need to be demonstrated. METHODS: We designed a cluster randomized feasibility trial to determine the effectiveness, acceptability, appropriateness, feasibility, and budget impact of two models for integrating a HPV-based CCSPT program into family planning (FP) services in Malawi: model 1 involves only clinic-based self-sampled HPV testing, whereas model 2 includes both clinic-based and community-based self-sampled HPV testing. Our algorithm involves self-collection of samples for HPV GeneXpert® testing, visual inspection with acetic acid for HPV-positive women to determine ablative treatment eligibility, and same-day thermal ablation for treatment-eligible women. Interventions will be implemented at 14 selected facilities. Our primary outcome will be the uptake of cervical cancer screening and family planning services during the 18 months of implementation, which will be measured through an Endline Household Survey. We will also conduct mixed methods assessments to understand the acceptability, appropriateness, and feasibility of the interventions, and a cost analysis to assess budget impact. DISCUSSION: Our trial will provide in-depth information on the implementation of clinic-only and clinic-and-community models for integrating self-sampled HPV testing CCSPT with FP services in Malawi. Findings will provide valuable insight for policymakers and implementers in Malawi and other resource-limited settings with high cervical cancer burden. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04286243 . Registered on February 26, 2020.

HPV prevalence in women attending cervical screening in rural Malawi using the cartridge-based Xpert® HPV assay.

BACKGROUND AND OBJECTIVES: Early experience with Cepheid Xpert® HPV assay (Xpert® HPV) suggests that its quick turnaround time and ease of application might make it a relevant contender for routine use in low and middle income countries (LMICs). In the context of a cervical screening service in rural Malawi, we aimed to assess practicalities of local laboratory testing with Xpert® HPV and provide preliminary high-risk HPV (HR-HPV) prevalence data. STUDY DESIGN: Liquid-based cytology (LBC) specimens were collected from women attending cervical screening clinics in Nkhoma, Malawi. Xpert® HPV testing was carried out according to manufacturer's instructions. Partial genotyping results were obtained immediately (HPV 16, 18/45 and HR-HPV 'other'). Review of individual channel data provided further breakdown of other HR-HPV types into HPV 31 and related; HPV 51/59 and HPV 39 and related. RESULTS: Valid HR-HPV results were obtained from 750/763 samples. Most samples were from previously unscreened women, with 92.3% aged between 20 and 60 years. Overall HR-HPV positivity was 19.9%, with HR-HPV 'other' being more than twice as frequent as HPV 16 or HPV 18/45 and HPV 31-related (HPV 31, 33, 35, 52 or 58) most prevalent. Known HIV status was low (7.3%), but HR-HPV positivity in this group was much higher (43.4%). CONCLUSIONS: HR-HPV testing using Xpert® HPV was practical in a small rural laboratory. The rapid turnaround (within 2h) could facilitate a 'see and treat' programme. Partial genotyping allows assessment of risk beyond HPV 16/18. The high prevalence of HPV 31 and related types warrants further investigation.

Analysing risk factors of co-occurrence of schistosomiasis haematobium and hookworm using bivariate regression models: Case study of Chikwawa, Malawi.

Schistosomiasis and soil-transmitted helminth (STH) infections constitute a major public health problem in many parts of sub-Saharan Africa. In areas where prevalence of geo-helminths and schistosomes is high, co-infection with multiple parasite species is common, resulting in disproportionately elevated burden compared with single infections. Determining risk factors of co-infection intensity is important for better design of targeted interventions. In this paper, we examined risk factors of hookworm and S. haematobium co-infection intensity, in Chikwawa district, southern Malawi in 2005, using bivariate count models. Results show that hookworm and S. haematobium infections were much localised with small proportion of individuals harbouring more parasites especially among school-aged children. The risk of co-intensity with both hookworm and S. haematobium was high for all ages, although this diminished with increasing age, increased with fishing (hookworm: coefficient. = 12.29; 95% CI = 11.50-13.09; S. haematobium: 0.040; 95% CI = 0.0037, 3.832). Both infections were abundant in those with primary education (hookworm: coef. = 0.072; 95% CI = 0.056, 0.401 and S. haematobium: coef. = 0.286; 95% CI = 0.034, 0.538). However, much lower risk was observed for those who were farmers (hookworm: coef. = - 0.349, 95% CI = - 0.547,-0.150; S. haematobium: coef. - 0.239, 95% CI = - 0.406, - 0.072). In conclusion, our findings suggest that efforts to control helminths infection should be co-integrated and health promotion campaigns should be aimed at school-going children and adults who are in constant contact with water.

Exploring barriers to the delivery of cervical cancer screening and early treatment services in Malawi: some views from service providers.

BACKGROUND: Cervical cancer is the most common reproductive health cancer in Malawi. In most cases, women report to health facilities when the disease is in its advanced stage. In this study, we investigate service providers' perceptions about barriers for women to access cervical cancer screening and early treatment services in Malawi. METHODS: We conducted in-depth interviews with 13 district coordinators and 40 service providers of cervical cancer screening and early treatment services in 13 districts in Malawi. The study was conducted in 2012. The district coordinators helped the research team identify the health facilities which were providing cervical cancer screening and early treatment services. RESULTS: Almost all informants reported that cervical cancer was a major public health problem in their districts and that prevention efforts for this disease were being implemented. They were aware of the test and treat approach using visual inspection with acetic acid (VIA). They, however, said that the delivery of cervical cancer screening and early treatment services was compromised because of factors such as gross shortage of staff, lack of equipment and supplies, the lack of supportive supervision, and the use of male service providers. Informants added that the lack of awareness about the disease among community members, long distances to health facilities, the lack of involvement of husbands, and prevailing misperceptions about the disease (eg, that it is caused by the exposure to the VIA process) affect the uptake of these services. CONCLUSION: While progress has been made in the provision of cervical cancer screening and early treatment services in Malawi, a number of factors affect service delivery and uptake. There is a need to continue creating awareness among community members including husbands and also addressing identified barriers such as shortage of staff and supplies in order to improve uptake of services.

Zero adjusted models with applications to analysing helminths count data.

BACKGROUND: It is common in public health and epidemiology that the outcome of interest is counts of events occurrence. Analysing these data using classical linear models is mostly inappropriate, even after transformation of outcome variables due to overdispersion. Zero-adjusted mixture count models such as zero-inflated and hurdle count models are applied to count data when over-dispersion and excess zeros exist. Main objective of the current paper is to apply such models to analyse risk factors associated with human helminths (S. haematobium) particularly in a case where there's a high proportion of zero counts. METHODS: The data were collected during a community-based randomised control trial assessing the impact of mass drug administration (MDA) with praziquantel in Malawi, and a school-based cross sectional epidemiology survey in Zambia. Count data models including traditional (Poisson and negative binomial) models, zero modified models (zero inflated Poisson and zero inflated negative binomial) and hurdle models (Poisson logit hurdle and negative binomial logit hurdle) were fitted and compared. RESULTS: Using Akaike information criteria (AIC), the negative binomial logit hurdle (NBLH) and zero inflated negative binomial (ZINB) showed best performance in both datasets. With regards to zero count capturing, these models performed better than other models. CONCLUSION: This paper showed that zero modified NBLH and ZINB models are more appropriate methods for the analysis of data with excess zeros. The choice between the hurdle and zero-inflated models should be based on the aim and endpoints of the study.

Combining qualitative and quantitative evidence to determine factors leading to late presentation for antiretroviral therapy in Malawi.

BACKGROUND: Treatment seeking delays among people living with HIV have adverse consequences for outcome. Gender differences in treatment outcomes have been observed in sub-Saharan Africa. OBJECTIVE: To better understand antiretroviral treatment (ART) seeking behaviour in HIV-infected adults in rural Malawi. METHODS: Qualitative interviews with male and female participants in an ART cohort study at a treatment site in rural northern Malawi triangulated with analysis of baseline clinical and demographic data for 365 individuals attending sequentially for ART screening between January 2008 and September 2009. RESULTS: 43% of the cohort presented with late stage HIV disease classified as WHO stage 3/4. Respondents reported that women's frequency of testing, health awareness and commitment to children led to earlier ART uptake and that men's commitment to wider social networks of influence, masculine ideals of strength, and success with sexual and marital partners led them to refuse treatment until they were sick. Quantitative analysis of the screening cohort provided supporting evidence for these expressed views. Overall, male gender (adjusted OR 2.3, 95% CI1.3-3.9) and never being married (adjusted OR 4.1, 95% CI1.5-11.5) were risk factors for late presentation, whereas having ≥3 dependent children was associated with earlier presentation (adjusted OR 0.31, 95% CI0.15-0.63), compared to those with no dependent children. CONCLUSION: Gender-specific barriers and facilitators operate throughout the whole process of seeking care. Further efforts to enrol men into care earlier should focus on the masculine characteristics that they value, and the risks to these of severe health decline. Our results emphasise the value of exploring as well as identifying behavioural correlates of late presentation.

The burden of selected chronic non-communicable diseases and their risk factors in Malawi: nationwide STEPS survey.

BACKGROUND: Chronic non-communicable diseases (NCDs) are becoming significant causes of morbidity and mortality, particularly in sub-Saharan African countries, although local, high-quality data to inform evidence-based policies are lacking. OBJECTIVES: To determine the magnitude of NCDs and their risk factors in Malawi. METHODS: Using the WHO STEPwise approach to chronic disease risk factor surveillance, a population-based, nationwide cross-sectional survey was conducted between July and September 2009 on participants aged 25-64 years. Socio-demographic and behaviour risk factors were collected in Step 1. Physical anthropometric measurements and blood pressure were documented in Step 2. Blood cholesterol and fasting blood glucose were measured in Step 3. RESULTS AND CONCLUSION: A total of 5,206 adults (67% females) were surveyed. Tobacco smoking, alcohol drinking and raised blood pressure (BP) were more frequent in males than females, 25% vs 3%, 30% vs 4% and 37% vs 29%. Overweight, physical inactivity and raised cholesterol were more common in females than males, 28% vs 16%, 13% vs 6% and 11% vs 6%. Tobacco smoking was more common in rural than urban areas 11% vs 7%, and overweight and physical inactivity more common in urban than rural areas 39% vs 22% and 24% vs 9%, all with p<0.05. Overall (both sexes) prevalence of tobacco smoking, alcohol consumption, overweight and physical inactivity was 14%, 17%, 22%, 10% and prevalence of raised BP, fasting blood sugar and cholesterol was 33%, 6% and 9% respectively. These data could be useful in the formulation and advocacy of NCD policy and action plan in Malawi.

High accuracy of home-based community rapid HIV testing in rural Malawi.

OBJECTIVE: To assess the performance of rapid HIV antibody tests when used as part of a home-based community wide counseling and testing strategy in northern Malawi. DESIGN: A cross-sectional population survey of HIV infection, 2007 to 2008. METHODS: Adults aged 15 years or older in a demographic surveillance area were counseled and then offered an HIV test at their home by government-certified counselors. Two initial rapid tests (Determine and Uni-Gold) were performed on all samples and a third, tie-breaker test (SD Bioline) used to resolve discordant results. All people who wanted to know were posttest-counseled and informed of their results with referral to local clinical services if found to be HIV-positive. Laboratory quality control comprised retesting all positive and every tenth negative venous blood sample collected. RESULTS: A total of 10,819 adults provided venous blood samples for HIV testing, of whom 7.5% (813) were HIV-positive. The accuracy of the parallel testing strategy used was high with 99.6% sensitivity, 100.0% specificity, 99.9% positive predictive value, and 99.9% negative predictive value. CONCLUSION: Face-to-face rapid testing by health personnel with minimum training at the client's home performs well when used on a wide scale in the community setting.

Mycobacterial purified protein derivatives stimulate innate immunity: Malawians show enhanced tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-10 responses compared to those of adolescents in the United Kingdom.

To investigate the role of innate immunity in variable efficacy of Mycobacterium bovis BCG vaccination in Malawi and the United Kingdom, we examined 24-h tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-10 responses to mycobacterial purified protein derivatives (PPDs). The rank order in stimulatory potency for different PPDs was the same for all three cytokines. Before vaccination Malawians made higher pro- and anti-inflammatory responses than did United Kingdom subjects. Fewer than 5% of United Kingdom subjects made IL-10 in response to any PPD, compared to 19 to 57% responders among Malawians. Priming for regulatory IL-10 may contribute to the smaller increase in gamma interferon responses in Malawians compared to United Kingdom subjects following BCG vaccination.