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.

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.

Assessment of water, sanitation and hygiene interventions in response to an outbreak of typhoid fever in Neno District, Malawi.

On May 2, 2009 an outbreak of typhoid fever began in rural villages along the Malawi-Mozambique border resulting in 748 illnesses and 44 deaths by September 2010. Despite numerous interventions, including distribution of WaterGuard (WG) for in-home water treatment and education on its use, cases of typhoid fever continued. To inform response activities during the ongoing Typhoid outbreak information on knowledge, attitudes, and practices surrounding typhoid fever, safe water, and hygiene were necessary to plan future outbreak interventions. In September 2010, a survey was administered to female heads in randomly selected households in 17 villages in Neno District, Malawi. Stored household drinking water was tested for free chlorine residual (FCR) levels using the N,N diethyl-p-phenylene diamine colorimetric method (HACH Company, Loveland, CO, USA). Attendance at community-wide educational meetings was reported by 56% of household respondents. Respondents reported that typhoid fever is caused by poor hygiene (77%), drinking unsafe water (49%), and consuming unsafe food (25%), and that treating drinking water can prevent it (68%). WaterGuard, a chlorination solution for drinking water treatment, was observed in 112 (56%) households, among which 34% reported treating drinking water. FCR levels were adequate (FCR ≥ 0.2 mg/L) in 29 (76%) of the 38 households who reported treatment of stored water and had stored water available for testing and an observed bottle of WaterGuard in the home. Soap was observed in 154 (77%) households, among which 51% reported using soap for hand washing. Educational interventions did not reach almost one-half of target households and knowledge remains low. Despite distribution and promotion of WaterGuard and soap during the outbreak response, usage was low. Future interventions should focus on improving water, sanitation and hygiene knowledge, practices, and infrastructure. Typhoid vaccination should be considered.

Safety of a killed oral cholera vaccine (Shanchol) in pregnant women in Malawi: an observational cohort study.

BACKGROUND: Pregnancy increases the risk of harmful effects from cholera for both mothers and their fetuses. A killed oral cholera vaccine, Shanchol (Shantha Biotechnics, Hydrabad, India), can protect against the disease for up to 5 years. However, cholera vaccination campaigns have often excluded pregnant women because of insufficient safety data for use during pregnancy. We did an observational cohort study to assess the safety of Shanchol during pregnancy. METHODS: This observational cohort study was done in two adjacent districts (Nsanje and Chikwawa) in Malawi. Individuals older than 1 year in Nsanje were offered oral cholera vaccine during a mass vaccination campaign between March 30 and April 30, 2015, but no vaccines were administered in Chikwawa. We enrolled women who were exposed to oral cholera vaccine during pregnancy in Nsanje district, and women who were pregnant in Chikwawa district (and thus not exposed to oral cholera vaccine) during the same period. The primary endpoint of our analysis was pregnancy loss (spontaneous miscarriage or stillbirth), and the secondary endpoints were neonatal deaths and malformations. We evaluated these endpoints using log-binomial regression, adjusting for the imbalanced baseline characteristics between the groups. This study is registered with ClinicalTrials.gov, number NCT02499172. FINDINGS: We recruited 900 women exposed to oral cholera vaccine and 899 women not exposed to the vaccine between June 16 and Oct 10, 2015, and analysed 835 in each group. 361 women exposed to the vaccine and 327 not exposed to the vaccine were recruited after their pregnancies had ended. The incidence of pregnancy loss was 27·54 (95% CI 18·41-41·23) per 1000 pregnancies among those exposed to the vaccine and 21·56 (13·65-34·04) per 1000 among those not exposed. The adjusted relative risk for pregnancy loss among those exposed to oral cholera vaccine was 1·24 (95% CI 0·64-2·43; p=0·52) compared with those not exposed to the vaccine. The neonatal mortality rate was 11·78 (95% CI 5·92-23·46) per 1000 livebirths for infants whose mothers were exposed to oral cholera vaccine versus 8·91 (4·02-19·77) per 1000 livebirths for infants whose mothers were not exposed to the vaccine (crude relative risk 1·32, 95% CI 0·46-3·84; p=0·60). Only three newborn babies had malformations, two in the vaccine exposure group and one in the no-exposure group, yielding a relative risk of 2·00 (95% CI 0·18-22·04; p=0·57), although this estimate is unreliable because of the small number of outcomes. INTERPRETATION: Our study provides evidence that fetal exposure to oral cholera vaccine confers no significantly increased risk of pregnancy loss, neonatal mortality, or malformation. These data, along with findings from two retrospective studies, support use of oral cholera vaccine in pregnant women in cholera-affected regions. FUNDING: Bill & Melinda Gates Foundation.

Predictors of Uptake and Timeliness of Newly Introduced Pneumococcal and Rotavirus Vaccines, and of Measles Vaccine in Rural Malawi: A Population Cohort Study.

BACKGROUND: Malawi introduced pneumococcal conjugate vaccine (PCV13) and monovalent rotavirus vaccine (RV1) in 2011 and 2012 respectively, and is planning the introduction of a second-dose measles vaccine (MV). We assessed predictors of availability, uptake and timeliness of these vaccines in a rural Malawian setting. METHODS: Commencing on the first date of PCV13 eligibility we conducted a prospective population-based birth cohort study of 2,616 children under demographic surveillance in Karonga District, northern Malawi who were eligible for PCV13, or from the date of RV1 introduction both PCV13 and RV1. Potential predictors of vaccine uptake and timeliness for PCV13, RV1 and MV were analysed respectively using robust Poisson and Cox regression. RESULTS: Vaccine coverage was high for all vaccines, ranging from 86.9% for RV1 dose 2 to 95.4% for PCV13 dose 1. Median time delay for PCV13 dose 1 was 17 days (IQR 7-36), 19 days (IQR 8-36) for RV1 dose 1 and 20 days (IQR 3-46) for MV. Infants born to lower educated or farming mothers and those living further away from the road or clinic were at greater risk of being not fully vaccinated and being vaccinated late. Delays in vaccination were also associated with non-facility birth. Vaccine stock-outs resulted in both a delay in vaccine timeliness and in a decrease in completion of schedule. CONCLUSION: Despite high vaccination coverage in this setting, delays in vaccination were common. We identified programmatic and socio-demographic risk factors for uptake and timeliness of vaccination. Understanding who remains most vulnerable to be unvaccinated allows for focussed delivery thereby increasing population coverage and maximising the equitable benefits of universal vaccination programmes.

Lessons and challenges for measles control from unexpected large outbreak, Malawi.

Despite high reported coverage for routine and supplementary immunization, in 2010 in Malawi, a large measles outbreak occurred that comprised 134,000 cases and 304 deaths. Although the highest attack rates were for young children (2.3%, 7.6%, and 4.5% for children <6, 6-8, and 9-11 months, respectively), persons >15 years of age were highly affected (1.0% and 0.4% for persons 15-19 and >19 years, respectively; 28% of all cases). A survey in 8 districts showed routine coverage of 95.0% for children 12-23 months; 57.9% for children 9-11 months; and 60.7% for children covered during the last supplementary immunization activities in 2008. Vaccine effectiveness was 83.9% for 1 dose and 90.5% for 2 doses. A continuous accumulation of susceptible persons during the past decade probably accounts for this outbreak. Countries en route to measles elimination, such as Malawi, should improve outbreak preparedness. Timeliness and the population chosen are crucial elements for reactive campaigns.

A retrospective survey of HIV drug resistance among patients 1 year after initiation of antiretroviral therapy at 4 clinics in Malawi.

In 2004, Malawi began scaling up its national antiretroviral therapy (ART) program. Because of limited treatment options, population-level surveillance of acquired human immunodeficiency virus drug resistance (HIVDR) is critical to ensuring long-term treatment success. The World Health Organization target for clinic-level HIVDR prevention at 12 months after ART initiation is ≥ 70%. In 2007, viral load and HIVDR genotyping was performed in a retrospective cohort of 596 patients at 4 ART clinics. Overall, HIVDR prevention (using viral load ≤ 400 copies/mL) was 72% (95% confidence interval [CI], 67%-77%; range by site, 60%-83%) and detected HIVDR was 3.4% (95% CI, 1.8%-5.8%; range by site, 2.5%-4.7%). Results demonstrate virological suppression and HIVDR consistent with previous reports from sub-Saharan Africa. High rates of attrition because of loss to follow-up were noted and merit attention.

Prevalence of HIV drug resistance before and 1 year after treatment initiation in 4 sites in the Malawi antiretroviral treatment program.

Since 2004, the Malawi antiretroviral treatment (ART) program has provided a public health-focused system based on World Health Organization clinical staging, standardized first-line ART regimens, limited laboratory monitoring, and no patient-level monitoring of human immunodeficiency virus drug resistance (HIVDR). The Malawi Ministry of Health conducts periodic evaluations of HIVDR development in prospective cohorts at sentinel clinics. We evaluated viral load suppression, HIVDR, and factors associated with HIVDR in 4 ART sites at 12-15 months after ART initiation. More than 70% of patients initiating ART had viral suppression at 12 months. HIVDR prevalence (6.1%) after 12 months of ART was low and largely associated with baseline HIVDR. Better follow-up, removal of barriers to on-time drug pickups, and adherence education for patients 16-24 years of age may further prevent HIVDR.

Lack of decline in childhood malaria, Malawi, 2001-2010.

In some areas of Africa, health facility data have indicated declines in malaria that might have resulted from increasingly effective control programs. Most such reports have been from countries where malaria transmission is highly seasonal or of modest intensity. In Malawi, perennial malaria transmission is intense, and malaria control measures have been scaled up during the past decade. We examined health facility data for children seen as outpatients and parasitemia-positive children hospitalized with cerebral malaria in a large national hospital. The proportion of Plasmodium falciparum-positive slides among febrile children at the hospital declined early in the decade, but no further reductions were observed after 2005. The number of admissions for cerebral malaria did not differ significantly by year. Continued surveillance for malaria is needed to evaluate the effects of the increased malaria control efforts.

Developing national treatment policy for falciparum malaria in Africa: Malawi experience.

The emergence and spread across sub-Saharan Africa of Plasmodium falciparum resistant to the inexpensive antimalarials chloroquine and sulfadoxine-pyrimethamine has worsened the health and hampered the socio-economic development of affected countries, a situation that calls for urgent review of malaria treatment policies in these countries. The Roll Back Malaria (RBM) initiative promotes strong partnerships for implementing effective malaria control measures. The development of clear policies to guide such implementation at country level offers a way of assessing the achievement of set milestones in this collaborative venture. In this article we describe the policy development process for the treatment of falciparum malaria in Africa, based on experience in Malawi, where the first-line drug treatment was recently changed from sulfadoxine-pyrimethamine to an artemisinin combination therapy.

Communicable disease control programmes in Malawi.

A series of half-day meetings were held between the Malawi National TB Control Programme and the other seven disease control programmes housed in the Community Health Science Unit (CHSU) to look at the structure and function of these programmes. Data were collected into a structured proforma on human resources, sources of international funding, policies and disease control activities, supportive activities, management organization, monitoring and evaluation and operational research. A number of constraints were identified, particularly in the areas of technical supervision, monitoring and evaluation and operational research. Serious consideration should be given to allow CHSU to have a more centralised and unifying role, with the aim of creating a more efficient and better-funded national communicable disease control service.