The causal effect of a family planning intervention on women's contraceptive use and birth spacing.

Studies have suggested that improving access to family planning (FP) may improve contraceptive use and reduce fertility. However, high-quality evidence, particularly from randomized implementation trials, of the effect of FP programs and interventions on longer-term fertility and birth spacing is lacking. We conduct a nonblinded, randomized, controlled trial to assess the causal impact of improved access to FP on contraceptive use and pregnancy spacing in Lilongwe, Malawi. A total of 2,143 married women aged 18 to 35 who were either pregnant or had recently given birth were recruited through home visits between September 2016 and January 2017 and were randomly assigned to an intervention arm or a control arm. The intervention arm received four services over a 2-y period: 1) up to six FP counseling sessions; 2) free transportation to an FP clinic; 3) free FP services at the clinic or financial reimbursement for FP services obtained elsewhere; and 4) treatment for contraceptive-related side effects. Contraceptive use after 2 y of intervention exposure increased by 5.9 percentage points, mainly through an increased use of contraceptive implants. The intervention group's hazard of pregnancy was 43.5% lower 24 mo after the index birth. Our results highlight the positive impact of increased access to FP on a woman's contraceptive use. In addition, we show that exposure to the FP intervention led to a prolongation of birth intervals among intervention women relative to control women and increased her control over birth spacing and postpartum fertility, which, in turn, may contribute to her longer-term health and well-being.

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.

Evaluation of Intussusception after Monovalent Rotavirus Vaccination in Africa.

BACKGROUND: Postlicensure evaluations have identified an association between rotavirus vaccination and intussusception in several high- and middle-income countries. We assessed the association between monovalent human rotavirus vaccine and intussusception in lower-income sub-Saharan African countries. METHODS: Using active surveillance, we enrolled patients from seven countries (Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia, and Zimbabwe) who had intussusception that met international (Brighton Collaboration level 1) criteria. Rotavirus vaccination status was confirmed by review of the vaccine card or clinic records. The risk of intussusception within 1 to 7 days and 8 to 21 days after vaccination among infants 28 to 245 days of age was assessed by means of the self-controlled case-series method. RESULTS: Data on 717 infants who had intussusception and confirmed vaccination status were analyzed. One case occurred in the 1 to 7 days after dose 1, and 6 cases occurred in the 8 to 21 days after dose 1. Five cases and 16 cases occurred in the 1 to 7 days and 8 to 21 days, respectively, after dose 2. The risk of intussusception in the 1 to 7 days after dose 1 was not higher than the background risk of intussusception (relative incidence [i.e., the incidence during the risk window vs. all other times], 0.25; 95% confidence interval [CI], <0.001 to 1.16); findings were similar for the 1 to 7 days after dose 2 (relative incidence, 0.76; 95% CI, 0.16 to 1.87). In addition, the risk of intussusception in the 8 to 21 days or 1 to 21 days after either dose was not found to be higher than the background risk. CONCLUSIONS: The risk of intussusception after administration of monovalent human rotavirus vaccine was not higher than the background risk of intussusception in seven lower-income sub-Saharan African countries. (Funded by the GAVI Alliance through the CDC Foundation.).

Cost-effectiveness of a reactive oral cholera immunization campaign using Shanchol™ in Malawi.

BACKGROUND: Oral cholera vaccines (OCV) have been recommended as additional measures for the prevention of cholera. However, little is known about the cost-effectiveness of OCV use in sub-Saharan Africa, particularly in reactive outbreak contexts. This study aimed to investigate the cost-effectiveness of the use of OCV Shanchol in response to a cholera outbreak in the Lake Chilwa area, Malawi. METHODS: The Excel-based Vaccine Introduction Cost-Effectiveness model was used to assess the cost-effectiveness ratios with and without indirect protection. Model input parameters were obtained from cost evaluations and epidemiological studies conducted in Malawi and published literature. One-way sensitivity and threshold analyses of cost-effectiveness ratios were performed. RESULTS: Compared with the reference scenario i.e. treatment of cholera cases, the immunization campaign would have prevented 636 and 1 020 cases of cholera without and with indirect protection, respectively. The cost-effectiveness ratios were US$19 212 per death, US$500 per case, and US$738 per DALY averted without indirect protection. They were US$10 165 per death, US$264 per case, and US$391 per DALY averted with indirect protection. The net cost per DALY averted was sensitive to four input parameters, including case fatality rate, duration of immunity (vaccine's protective duration), discount rate and cholera incidence. CONCLUSION: Relative to the Malawi gross domestic product per capita, the reactive OCV campaign represented a cost-effective intervention, particularly when considering indirect vaccine effects. Results will need to be assessed in other settings, e.g., during campaigns implemented directly by the Ministry of Health rather than by international partners.

Risk Factors Associated With Increased Mortality From Intussusception in African Infants.

OBJECTIVES: Morbidity and mortality from intussusception, the leading cause of bowel obstruction in infants, is higher in Africa than in other regions of the world, but the reasons have not been well examined. We sought to identify risk and protective factors associated with death or intestinal resection following intussusception. METHODS: Infants with intussusception from 7 sub-Saharan African countries (Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia, and Zimbabwe) were enrolled through active, hospital-based surveillance from February 2012 to December 2016. We examined demographic, clinical, and socioeconomic factors associated with death or intestinal resection following intussusception, using multivariable logistic regression. RESULTS: A total of 1017 infants <1 year of age with intussusception were enrolled. Overall, 13% of children (133/1017) died during the hospitalization, and 48% (467/966) required intestinal resection. In multivariable analyses, female sex [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.2-3.3], longer duration of symptoms before presentation (OR 1.1; 95% CI 1.0-1.2), and undergoing intestinal resection (OR 3.4; 95% CI 1.9-6.1) were associated with death after intussusception. Diagnosis by ultrasound or enema (OR 0.4; 95% CI 0.3-0.7), and employment of a household member (OR 0.7; 95% CI 0.4-1.0) were protective against intestinal resection. CONCLUSIONS: Delays in hospital presentation and female sex were significantly associated with death, whereas higher socioeconomic status and availability of radiologic diagnosis reduced likelihood of undergoing resection. Efforts should be intensified to improve the awareness, diagnosis, and management of intussusception in sub-Saharan African countries to reduce morbidity and mortality from intussusception in these resource-limited settings.

Adolescent and covert family planning users' experiences self-injecting contraception in Uganda and Malawi: implications for waste disposal of subcutaneous depot medroxyprogesterone acetate.

BACKGROUND: Self-administered subcutaneous depot medroxyprogesterone acetate (DMPA-SC) is poised to increase access to contraception; however, governments are concerned about the waste management of used units. Self-injectors in Malawi and Uganda are currently instructed to store used units in containers and return them to health workers for disposal. However, this may not be feasible in low-resource settings, especially for younger or covert self-injectors. We describe adolescent (15-19 years) and adult (20-49 years) self-injectors' disposal experiences in Uganda and Malawi. When possible, we compare covert and overt users' experiences. METHODS: We conducted cross-sectional qualitative studies in 2019 with 50 self-injectors in Uganda and 60 in Malawi. We purposively selected approximately half adolescents and included those trained by clinic-based providers and community health workers. We conducted semi-structured interviews and thematic data analysis and compared the findings across settings. RESULTS: Just under half of both samples were adolescents, substantially more of whom were covert users in Uganda (68%) than Malawi (~ 10%). Most participants reported being told to store used units in a container and return them to health workers. About two-thirds of Uganda participants had disposed of at least one unit by the interview, most commonly returning them to health workers. Over one-third of Malawi participants had disposed of at least one unit by the interview, slightly more disposed into latrines compared to returning to health workers. Participants in both settings reported compliance with health workers' disposal instructions as a primary reason for their disposal method. One-fifth of Uganda participants, mostly adolescent covert users, and one-quarter in Malawi said they were told they could dispose into latrines, and often did so. The majority in both settings said they would prefer to dispose units in latrines because they worried about needlestick injuries to others and because it was convenient. Some Uganda adolescent covert users felt returning units to health workers was challenging due to privacy concerns. CONCLUSIONS: While most self-injectors disposed of used units as instructed, findings from both studies suggest that returning units to health workers is not preferred and may not be feasible for some adolescent covert users. More convenient disposal solutions should be identified.

Health literacy among Malawian HIV-positive youth: a qualitative needs assessment and conceptualization.

Despite growing evidence of the significance of health literacy in managing and coping with acquired immune deficiency syndrome (HIV), it is not yet an integrated part of HIV/AIDS-related health promotion research and practice in Africa. This article contributes to addressing the gap in research on health literacy and HIV in Sub-Saharan Africa. We aimed to assess health literacy-related needs of young people living with HIV (YPLHIV) and adapt existing health literacy frameworks to the context of HIV/AIDS in Malawi. We used focus group discussions to collect data from a sample of the membership of the national association of YPLHIV. Twenty-four HIV-positive youth (18-29 years) participated in focus group discussions. Participants came from three regions of Malawi. Additionally, we conducted three in-depth interviews with key informants. We used a thematic framework approach to analyse data in MAXQDA. We contextualized definitions of four dimensions of health literacy: functional, interactive, critical and distributed health literacy, which we used as an a priori analytical framework. To further contextualize the framework, we revised it iteratively throughout the analysis process. We identified the need for comprehensive information about HIV and sexual reproductive health, skills to interact with healthcare providers and navigate the health system, and skills to appraise information from different sources, among others. The identified needs were translated into nine action recommendations for the national association of YPLHIV, and with relevance within the wider HIV sector in Malawi and beyond. We found that the dimensions in our analytical framework operate on the individual, system and public policy levels.

Oral cholera vaccine in cholera prevention and control, Malawi.

PROBLEM: With limited global supplies of oral cholera vaccine, countries need to identify priority areas for vaccination while longer-term solutions, such as water and sanitation infrastructure, are being developed. APPROACH: In 2017, Malawi integrated oral cholera vaccine into its national cholera control plan. The process started with a desk review and analysis of previous surveillance and risk factor data. At a consultative meeting, researchers, national health and water officials and representatives from nongovernmental and international organizations reviewed the data and local epidemiological knowledge to determine priority districts for oral cholera vaccination. The final stage was preparation of an application to the global oral cholera vaccine stockpile for non-emergency use. LOCAL SETTING: Malawi collects annual data on cholera and most districts have reported cases at least once since the 1970s. RELEVANT CHANGES: The government's application for 3.2 million doses of vaccine to be provided over 20 months in 12 districts was accepted in April 2017. By April 2018, over 1 million doses had been administered in five districts. Continuing surveillance in districts showed that cholera outbreaks were notably absent in vaccinated high-risk areas, despite a national outbreak in 2017-2018. LESSONS LEARNT: Augmenting advanced mapping techniques with local information helped us extend priority areas beyond those identified as high-risk based on cholera incidence reported at the district level. Involvement of the water, sanitation and hygiene sectors is key to ensuring that short-term gains from cholera vaccine are backed by longer-term progress in reducing cholera transmission.

Alcohol policies in Malawi: inclusion of WHO "best buy" interventions and use of multi-sectoral action.

BACKGROUND: Harmful use of alcohol is one of the most common risk factors for Non-Communicable Diseases and other health conditions such as injuries. World Health Organization has identified highly cost-effective interventions for reduction of alcohol consumption at population level, known as "best buy" interventions, which include tax increases, bans on alcohol advertising and restricted access to retailed alcohol. This paper describes the extent of inclusion of alcohol related "best buy" interventions in national policies and also describes the application of multi-sectoral action in the development of alcohol policies in Malawi. METHODS: The study was part of a multi-country research project on Analysis of Non-Communicable Disease Preventive Policies in Africa, which applied a qualitative case study design. Data were collected from thirty-two key informants through interviews. A review of twelve national policy documents that relate to control of harmful use of alcohol was also conducted. Transcripts were coded according to a predefined protocol followed by thematic content analysis. RESULTS: Only three of the twelve national policy documents related to alcohol included at least one "best buy" intervention. Multi-Sectoral Action was only evident in the development process of the latest alcohol policy document, the National Alcohol Policy. Facilitators for multi-sectoral action for alcohol policy formulation included: structured leadership and collaboration, shared concern over the burden of harmful use of alcohol, advocacy efforts by local non-governmental organisations and availability of some dedicated funding. Perceived barriers included financial constraints, high personnel turnover in different government departments, role confusion between sectors and some interference from the alcohol industry. CONCLUSIONS: Malawi's national legislations and policies have inadequate inclusion of the "best buy" interventions for control of harmful use of alcohol. Effective development and implementation of alcohol policies require structured organisation and collaboration of multi-sectoral actors. Sustainable financing mechanisms for the policy development and implementation processes should be considered; and the influence of the alcohol industry should be mitigated.

Pneumococcal Acquisition Among Infants Exposed to HIV in Rural Malawi: A Longitudinal Household Study.

The prevalence of Streptococcus pneumoniae (pneumococcus) carriage is higher in adults who are infected with human immunodeficiency virus (HIV) than in adults who are not. We hypothesized that infants exposed to HIV become carriers of nasopharyngeal pneumococcus earlier and more frequently than infants who are not exposed to HIV. We compared infant pneumococcal acquisition by maternal HIV status and household exposure in Karonga District, Malawi, in 2009-2011, before the introduction of pneumococcal conjugate vaccine. Nasopharyngeal swabs were collected every 4-6 weeks in the first year of life from infants with known HIV-exposure status, their mothers, and other household members. We studied infant pneumococcal acquisition by maternal HIV status, serotype-specific household exposure, and other risk factors, including seasonality. We recruited 54 infants who were exposed to HIV and 131 infants who were not. There was no significant difference in pneumococcal acquisition by maternal HIV status (adjusted rate ratio (aRR) = 1.00, 95% confidence interval (CI): 0.87, 1.15). Carriage by the mother was associated with greater acquisition of the same serotype (aRR = 3.09, 95% CI: 1.47, 6.50), but the adjusted population attributable fraction was negligible (1.9%, 95% CI: 0.0, 4.3). Serotype-specific exposure to children under 5 years of age was associated with higher acquisition (aRR = 4.30, 95% CI: 2.80, 6.60; adjusted population attributable fraction = 8.8%, 95% CI: 4.0, 13.4). We found no evidence to suggest that maternal HIV infection would affect the impact of pneumococcal vaccination on colonization in this population.

Determinants of time to antiretroviral treatment initiation and subsequent mortality on treatment in a cohort in rural northern Malawi.

BACKGROUND: To optimise care HIV patients need to be promptly initiated on antiretroviral therapy (ART) and subsequently retained on treatment. In this study we report on the interval between enrolment and treatment initiation, and investigate subsequent attrition and mortality of patients on ART at a rural clinic in Malawi. METHODS: HIV-positive individuals were recruited to a cohort study between January 2008 and August 2011 at Chilumba Rural Hospital (CRH). Outcomes were ascertained, up to 7 years after enrolment, through follow-up and by linkage to ART registers and the Karonga Health and Demographic Surveillance System (KHDSS). Kaplan-Meier methods and Cox regression were used to examine ART initiation after enrolment, mortality after ART initiation, and attrition after ART initiation. RESULTS: Of the 617 individuals recruited, 523 initiated ART between January 2008 and January 2015. Median time from HIV testing to commencement of ART was 59 days (IQR: 10-330). By a year after enrolment 74.2 % (95 % CI 70.6-77.7 %) had initiated ART. Baseline clinical data at ART initiation and data on attrition was only available for the 438 individuals who initiated ART during active follow-up, between January 2008 and August 2011. Of these individuals, 6 were missing Ministry of Health numbers, leaving 432 included in analyses of attrition and mortality. At 4 years after ART initiation 71.3 % (95 % CI 65.7-76.2 %) of these patients were retained on treatment at the CRH and 17.2 % (95 % CI 13.8-21.4 %) had died. Participants who had a lower CD4 count at enrolment (≤350 cells/µl), enrolled in 2008, or tested for HIV at the CRH rather than through serosurveys, initiated treatment faster. Once on treatment, mortality rates were higher in patients who were HIV tested at the CRH, male, older (≥35 years), missing a CD4 count, or underweight (BMI < 18.5) at ART initiation. CONCLUSIONS: Through linkage to the KHDSS and ART registers it was possible to continue follow-up beyond the end of the initial cohort study. Annual mortality after ART initiation remained considerable over a period of 4 years. Greater access to HIV and CD4 testing alongside initiation at higher CD4 counts, as planned in the test and treat strategy, could reduce this mortality.

Factors Influencing Delayed Health Care Seeking Among Pulmonary Tuberculosis Suspects in Rural Communities in Ntcheu District, Malawi.

Delayed diagnosis and treatment of tuberculosis (TB) among individuals suspected of having TB may lead to continued transmission of Mycobacterium tuberculosis in communities, higher mortality rates, and increase in government health expenditure because of prolonged illness due to late diagnosis and treatment initiation. The study explored factors leading to delayed health care seeking among individuals living in Ntcheu District, Malawi. Two key informant interviews, 16 in-depth interviews, and three focus group discussions were conducted. Participants were aged 18 years and older and never had TB. Data were analyzed using content analysis and factors were identified: inadequate knowledge about cause and transmission of TB, low self-awareness of personal risk to TB, cultural and traditional beliefs about sources of TB, stigma, and strong belief in witchcraft as a cause of illness. The TB Control Program needs to invest in social mobilization and education of communities to mitigate early health care seeking.

Using patient-held records to evaluate contraceptive use in Malawi.

OBJECTIVE: To investigate a method of using patient-held records to collect contraception data in Malawi, that could be used to explore contraceptive discontinuation and method switching. METHODS: In 2012, all 7393 women aged 15 to 49 years living in the area covered by the Karonga demographic surveillance site were offered a family planning card, which was attached to the woman's health passport - a patient-held medical record. Health-care providers were trained to use the cards to record details of contraception given to women. During the study, providers underwent refresher training sessions and received motivational text messages to improve data completeness. After one year, the family planning cards were collected for analysis. FINDINGS: Of the 7393 eligible women, 6861 (92.8%) received a family planning card and 4678 (63.3%) returned it after one year. Details of 87.3% (2725/3122) of contacts between health-care providers and the women had been recorded by health-care providers on either family planning cards or health passports. Lower-level health-care providers were more diligent at recording data on the family planning cards than higher-level providers. CONCLUSION: The use of family planning cards was an effective way of recording details of contraception provided by family planning providers. The involvement of health-care providers was key to the success of this approach. Data collected in this way should prove helpful in producing accurate estimates of method switching and the continuity of contraceptive use by women.

Potential barriers to healthcare in Malawi for under-five children with cough and fever: a national household survey.

Failure to access healthcare is an important contributor to child mortality in many developing countries. In a national household survey in Malawi, we explored demographic and socioeconomic barriers to healthcare for childhood illnesses and assessed the direct and indirect costs of seeking care. Using a cluster-sample design, we selected 2,697 households and interviewed 1,669 caretakers. The main reason for households not being surveyed was the absence of a primary caretaker in the household. Among 2,077 children aged less than five years, 504 episodes of cough and fever during the previous two weeks were reported. A trained healthcare provider was visited for 48.0% of illness episodes. A multivariate regression model showed that children from the poorest households (p = 0.02) and children aged > 12 months (p = 0.02) were less likely to seek care when ill compared to those living in wealthier households and children of higher age-group respectively. Families from rural households spent more time travelling compared to urban households (68.9 vs 14.1 minutes; p < 0.001). In addition, visiting a trained healthcare provider was associated with longer travel time (p < 0.001) and higher direct costs (p < 0.001) compared to visiting an untrained provider. Thus, several barriers to accessing healthcare in Malawi for childhood illnesses exist. Continued efforts to reduce these barriers are needed to narrow the gap in the health and healthcare equity in Malawi.

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.

G8 rotaviruses with conserved genotype constellations detected in Malawi over 10 years (1997-2007) display frequent gene reassortment among strains co-circulating in humans.

Rotavirus A, the most common cause of severe diarrhoea in children worldwide, occurs in five major VP7 (G) and VP4 (P) genotype combinations, comprising G1P[8], G2P[4], G3P[8], G4P[8] and G9P[8]. However, G8, a common bovine rotavirus genotype, has been reported frequently among children in African countries. Surveillance of rotavirus gastroenteritis conducted in a sentinel hospital in Blantyre, Malawi between 1997 and 2007 provided a rare opportunity to examine the whole genotype constellation of G8 strains and their evolution over time. A sample of 27 (9.0 %) of 299 G8 strains was selected to represent each surveillance year and a range of P genotypes, which shifted in predominance from P[6] to P[4] and P[8] during the study period. Following cell culture adaptation, whole genome sequencing demonstrated that the genetic background of 26 strains possessed the DS-1 genotype constellation. A single G8P[6] strain was a reassortant in which both NSP2 and NSP5 genes from strains with the Wa genotype constellation had been inserted into a strain with the DS-1 genotype background. Phylogenetic analysis suggested frequent reassortment among co-circulating strains with the DS-1 genotype constellation. Little evidence was identified to suggest the introduction of contemporary bovine rotavirus genes into any of the 27 G8 strains examined. In conclusion, Malawian G8 strains are closely related to other human strains with the DS-1 genotype constellation. They have evolved over the last decade through genetic reassortment with other human rotaviruses, changing their VP4 genotypes while maintaining a conserved genotype constellation for the remaining structural and non-structural proteins.

Effect of human rotavirus vaccine on severe diarrhea in African infants.

BACKGROUND: Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children. METHODS: We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine--the pooled vaccine group--or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale. RESULTS: A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group. CONCLUSIONS: Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.)

CISH and susceptibility to infectious diseases.

BACKGROUND: The interleukin-2-mediated immune response is critical for host defense against infectious pathogens. Cytokine-inducible SRC homology 2 (SH2) domain protein (CISH), a suppressor of cytokine signaling, controls interleukin-2 signaling. METHODS: Using a case-control design, we tested for an association between CISH polymorphisms and susceptibility to major infectious diseases (bacteremia, tuberculosis, and severe malaria) in blood samples from 8402 persons in Gambia, Hong Kong, Kenya, Malawi, and Vietnam. We had previously tested 20 other immune-related genes in one or more of these sample collections. RESULTS: We observed associations between variant alleles of multiple CISH polymorphisms and increased susceptibility to each infectious disease in each of the study populations. When all five single-nucleotide polymorphisms (SNPs) (at positions -639, -292, -163, +1320, and +3415 [all relative to CISH]) within the CISH-associated locus were considered together in a multiple-SNP score, we found an association between CISH genetic variants and susceptibility to bacteremia, malaria, and tuberculosis (P=3.8x10(-11) for all comparisons), with -292 accounting for most of the association signal (P=4.58x10(-7)). Peripheral-blood mononuclear cells obtained from adult subjects carrying the -292 variant, as compared with wild-type cells, showed a muted response to the stimulation of interleukin-2 production--that is, 25 to 40% less CISH expression. CONCLUSIONS: Variants of CISH are associated with susceptibility to diseases caused by diverse infectious pathogens, suggesting that negative regulators of cytokine signaling have a role in immunity against various infectious diseases. The overall risk of one of these infectious diseases was increased by at least 18% among persons carrying the variant CISH alleles.

Detection and molecular characterisation of noroviruses in hospitalised children in Malawi, 1997-2007.

Despite the increasing recognition of noroviruses as major pathogens associated with community-acquired diarrhoea in children, there are few studies from Africa. Long-term surveillance studies of rotavirus gastroenteritis in Malawian children have provided an opportunity to undertake a study of the importance and epidemiological features of norovirus infection in this population. Faecal specimens were collected from children <5 years of age admitted to hospital with acute diarrhoea, as well as from a comparison group of diarrhoea-free children, in Blantyre, Malawi between 1997 and 2007. Norovirus was detected using real-time PCR and strains genotyped by nucleotide sequence analysis. Norovirus was detected in 220/1,941 (11.3%) faecal specimens, comprising genogroup GI (1.8%), GII (9.4%) and mixed GI/GII (0.1%). The median age of children with norovirus was 6 months (range, 0-48 months). Norovirus was detected throughout the year, with peaks at the end of the rainy season (March) and towards the end of the dry season (August-November). Norovirus GII.4 was the most commonly detected genotype accounting for 70% of strains characterised, followed by GII.2 (6%), GII.6 (4%) and GII.12 (4%). Sub typing of GII.4 noroviruses demonstrated local circulation of strains prior to their subsequent detection in association with global epidemics of gastroenteritis. The prevalence of norovirus in children without diarrhoea was similar to the level in cases. This largest study to date of norovirus infection in African children indicates the potential role of paediatric surveillance in predicting the emergence of norovirus strains with global epidemic potential.