Prevalence and incidence of transfusion-transmissible infections among blood donors in Malawi: A population-level study.

BACKGROUND: Voluntary non-remunerated blood donors (VNRBDs) are essential to sustain national blood supplies. Expanding testing capacity for the major transfusion-transmitted infections (TTI) is crucial to ensure safe blood products. Understanding trends in TTIs can inform prioritisation of resources. METHODS: We conducted a retrospective cohort data analysis of routine blood donation data collected from VNRBDs by the Malawi Blood Transfusion Service from January 2015 to October 2021. Variables included age, occupation; and screening results of TTIs (HIV, Hepatitis B and C, and syphilis). We estimated both prevalence and incidence per person-year for each TTI using longitudinal and spatial logistic regression models. RESULTS: Of the 213 626 donors, 204 920 (95.8%) donors were included in the final analysis. Most donors (77.4%) were males, baseline median age was 19.9 (IQR 18.0, 24.1), 70.9% were students, and over 80.0% were single at first donation. Overall TTI prevalence among donors was 10.7%, with HBV having the highest prevalence (3.4%), followed by syphilis (3.3%), then HIV (2.4%) and HCV (2.4%). Incidence per 1000 person-years for syphilis was 20.1 (19.0, 21.3), HCV was 18.4 (17.3, 19.5), HBV was 13.7 (12.8, 14.7), and HIV was 11.4 (10.6, 12.3). We noted geographical variations with the northern region having lower rates of both prevalence and incidence compared to central and southern regions. CONCLUSION: The individual TTI prevalence and incidence rates from this study are consistent with Southern African regional estimates. By identifying geographical variations of TTI prevalence and incidence, these findings could potentially inform prioritisation of blood collection efforts to optimise blood collection processes.

Systematic review of prevalence and risk factors of transfusion transmissible infections among blood donors, and blood safety improvements in Southern Africa.

Blood and blood products are listed as one of the essential medicines by the World Health Organization (WHO). In addition to inadequate supply, most sub-Saharan Africa (SSA) nations fail to meet their blood needs because many donated blood units are discarded because they are contaminated with transfusion-transmitted infections (TTIs). We sought to estimate the prevalence of TTIs, identify the risk factors for TTIs among blood donors, and identify the efforts and interventions that have been made to improve blood safety in Southern African nations, particularly the nations of the South African Development Community (SADC). We investigated the prevalence and risk factors for TTIs, blood safety interventions, and blood quality improvement in the SADC region from major PubMed/MEDLINE, Cochrane Library, and HINARI databases from 1 January 2011 to 31 April 2021. All investigations followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). In meta-analysis, we estimated the pooled TTIs prevalence and summarised the same using forest plots. A total of 180 articles published from the SSA region were identified covering our three targeted themes: TTI prevalence, risk factors for TTIs, and blood safety improvements. Of these 180 articles, only 27 (15%) focused on the SADC region. The overall pooled TTI prevalence estimate was 2.0% (95% CI: 1.0-3.0) and hepatitis B was the most prevalent TTI in the region (prevalence = 3.0; 95% CI: 2.0-5.0). The prevalence of HIV, HCV, and syphilis was 2.0% (95% CI: 1.0-4.0), 1.0% (95% CI: 0.0-2.0), and 2.0% (95% CI: 0.0-8.0), respectively. In general, replacement donors and first-time donors were more likely to be infected with TTIs than repeat donors. Twelve articles explored blood safety research in the region; however, they vary greatly highlighting the need for consistent and more comprehensive research. Few publications were identified that were from the SADC region, indicating lack of research or resources towards improving both quantity and quality of blood donation. TTI prevalence remains one of the highest in the world and blood safety recommendations vary across the region. More effort should be directed towards developing a cohesive regional blood transfusion policy and effective blood monitoring and evaluation strategies.

Effects of COVID-19 on Maternal and Neonatal Outcomes and Access to Antenatal and Postnatal Care, Malawi.

We used national facility-level data from all government hospitals in Malawi to examine the effects of the second and third COVID-19 waves on maternal and neonatal outcomes and access to care during September 6, 2020-October 31, 2021. The COVID-19 pandemic affected maternal and neonatal health not only through direct infections but also through disruption of the health system, which could have wider indirect effects on critical maternal and neonatal outcomes. In an interrupted time series analysis, we noted a cumulative 15.4% relative increase (63 more deaths) in maternal deaths than anticipated across the 2 COVID-19 waves. We observed a 41% decrease in postnatal care visits at the onset of the second COVID-19 wave and 0.2% by the third wave, cumulative to 36,809 fewer visits than anticipated. Our findings demonstrate the need for strengthening health systems, particularly in resource-constrained settings, to prepare for future pandemic threats.

Comparison of maternal and neonatal outcomes of COVID-19 before and after SARS-CoV-2 omicron emergence in maternity facilities in Malawi (MATSurvey): data from a national maternal surveillance platform.

BACKGROUND: Outcomes of omicron-associated COVID-19 in pregnancy have not been reported from low-resource settings, and data from sub-Saharan Africa before the emergence of omicron are scarce. Using a national maternal surveillance platform (MATSurvey), we aimed to compare maternal and neonatal outcomes of COVID-19 in Malawi during the omicron wave to the preceding waves of beta and delta. METHODS: All pregnant and recently pregnant patients, up to 42 days following delivery, admitted to 33 health-care facilities throughout Malawi with symptomatic, test-proven COVID-19 during the second (beta [B.1.351]: January to April, 2021), third (delta [B.1.617.2]: June to October, 2021), and fourth (omicron [B.1.1.529]: December 2021 to March, 2022) waves were included, with no age restrictions. Demographic and clinical features, maternal outcomes of interest (severe maternal outcome [a composite of maternal near-miss events and maternal deaths] and maternal death), and neonatal outcomes of interest (stillbirth and death during maternal stay in the health-care facility of enrolment) were compared between the fourth wave and the second and third waves using Fisher's exact test. Adjusted odds ratios (ORs) for maternal outcomes were estimated using mixed-effects logistic regression. FINDINGS: Between Jan 1, 2021, and March 31, 2022, 437 patients admitted to 28 health-care facilities conducting MATSurvey had symptoms of COVID-19. SARS-CoV-2 infection was confirmed in 261 patients; of whom 76 (29%) had a severe maternal outcome and 45 (17%) died. These two outcomes were less common during the fourth wave (omicron dominance) than the second wave (adjusted OR of severe maternal outcome: 3·96 [95% CI 1·22-12·83], p=0·022; adjusted OR of maternal death: 5·65 [1·54-20·69], p=0·0090) and the third wave (adjusted OR: 3·18 [1·03-9·80], p=0·044; adjusted OR: 3·52 [0·98-12·60], p=0·053). Shortness of breath was the only symptom associated with poor maternal outcomes of interest (p<0·0001), and was less frequently reported in the fourth wave (23%) than in the second wave (51%; p=0·0007) or third wave (50%; p=0·0004). The demographic characteristics and medical histories of patients were similar across the three waves. During the second and third waves, 12 (13%) of 92 singleton neonates were stillborn or died during maternal stay in the health-care facility of enrolment, compared with 0 of the 25 born in the fourth wave (p=0·067 vs preceding waves combined). INTERPRETATION: Maternal and neonatal outcomes from COVID-19 were less severe during the fourth wave of the SARS-CoV-2 pandemic in Malawi, during omicron dominance, than during the preceding beta and delta waves. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, and the National Institute for Health and Care Research. TRANSLATION: For the Chichewa translation of the abstract see Supplementary Materials section.

SARS-CoV-2 exposure in Malawian blood donors: an analysis of seroprevalence and variant dynamics between January 2020 and July 2021.

BACKGROUND: By August 2021, the COVID-19 pandemic has been less severe in sub-Saharan Africa than elsewhere. In Malawi, there have been three subsequent epidemic waves. We therefore aimed to describe the dynamics of SARS-CoV-2 exposure in Malawi. METHODS: We measured the seroprevalence of anti-SARS-CoV-2 antibodies amongst randomly selected blood transfusion donor sera in Malawi from January 2020 to July 2021 using a cross-sectional study design. In a subset, we also assessed in vitro neutralisation against the original variant (D614G WT) and the Beta variant. RESULTS: A total of 5085 samples were selected from the blood donor database, of which 4075 (80.1%) were aged 20-49 years. Of the total, 1401 were seropositive. After adjustment for assay characteristics and applying population weights, seropositivity reached peaks in October 2020 (18.5%) and May 2021 (64.9%) reflecting the first two epidemic waves. Unlike the first wave, both urban and rural areas had high seropositivity in the second wave, Balaka (rural, 66.2%, April 2021), Blantyre (urban, 75.6%, May 2021), Lilongwe (urban, 78.0%, May 2021), and Mzuzu (urban, 74.6%, April 2021). Blantyre and Mzuzu also show indications of the start of a third pandemic wave with seroprevalence picking up again in July 2021 (Blantyre, 81.7%; Mzuzu, 71.0%). More first wave sera showed in vitro neutralisation activity against the original variant (78% [7/9]) than the beta variant (22% [2/9]), while more second wave sera showed neutralisation activity against the beta variant (75% [12/16]) than the original variant (63% [10/16]). CONCLUSION: The findings confirm extensive SARS-CoV-2 exposure in Malawi over two epidemic waves with likely poor cross-protection to reinfection from the first on the second wave. The dynamics of SARS-CoV-2 exposure will therefore need to be taken into account in the formulation of the COVID-19 vaccination policy in Malawi and across the region. Future studies should use an adequate sample size for the assessment of neutralisation activity across a panel of SARS-CoV-2 variants of concern/interest to estimate community immunity.

Outcomes of critically ill patients with acute kidney injury in COVID-19 infection: an observational study.

BACKGROUND: Early reports indicate that AKI is common during COVID-19 infection. Different mortality rates of AKI due to SARS-CoV-2 have been reported, based on the degree of organic dysfunction and varying from public to private hospitals. However, there is a lack of data about AKI among critically ill patients with COVID-19. METHODS: We conducted a multicenter cohort study of 424 critically ill adults with severe acute respiratory syndrome (SARS) and AKI, both associated with SARS-CoV-2, admitted to six public ICUs in Brazil. We used multivariable logistic regression to identify risk factors for AKI severity and in-hospital mortality. RESULTS: The average age was 66.42 ± 13.79 years, 90.3% were on mechanical ventilation (MV), 76.6% were at KDIGO stage 3, and 79% underwent hemodialysis. The overall mortality was 90.1%. We found a higher frequency of dialysis (82.7% versus 45.2%), MV (95% versus 47.6%), vasopressors (81.2% versus 35.7%) (p < 0.001) and severe AKI (79.3% versus 52.4%; p = 0.002) in nonsurvivors. MV, vasopressors, dialysis, sepsis-associated AKI, and death (p < 0.001) were more frequent in KDIGO 3. Logistic regression for death demonstrated an association with MV (OR = 8.44; CI 3.43-20.74) and vasopressors (OR = 2.93; CI 1.28-6.71; p < 0.001). Severe AKI and dialysis need were not independent risk factors for death. MV (OR = 2.60; CI 1.23-5.45) and vasopressors (OR = 1.95; CI 1.12-3.99) were also independent risk factors for KDIGO 3 (p < 0.001). CONCLUSION: Critically ill patients with SARS and AKI due to COVID-19 had high mortality in this cohort. Mortality was largely determined by the need for mechanical ventilation and vasopressors rather than AKI severity.

Emergency and critical care services in Malawi: Findings from a nationwide survey of health facilities.

Background: Globally, critical illness causes up to 45 million deaths every year. The burden is highest in low-income countries such as Malawi. Critically ill patients require good quality, essential care in emergency departments and in hospital wards to avoid negative outcomes such as death. Little is known about the quality of care or the availability of necessary resources for emergency and critical care in Malawi. The aim of this study was to assess the availability of resources for emergency and critical care in Malawi using data from the Service Provision Assessment (SPA). Methods: We conducted a secondary data analysis of the SPA - a nationwide survey of all health facilities. We assessed the availability of resources for emergency and critical care using previously developed standards for hospitals in low-income countries. Each health facility received an availability score, calculated as the proportion of resources that were present. Resource availability was sub-divided into the seven a-priori defined categories of drugs, equipment, support services, emergency guidelines, infrastructure, training and routines. Results: Of the 254 indicators in the standards necessary for assessing the quality of emergency and critical care, SPA collected data for 102 (40.6%). Hospitals had a median resource availability score of 51.6% IQR (42.2-67.2) and smaller health facilities had a median of 37.5% (IQR 28.1-45.3). For the category of drugs, the hospitals' median score was 62.0% IQR (52.4-81.0), for equipment 51.9% IQR (40.7-66.7), support services 33.3% IQR (22.2-77.8) and emergency guidelines 33.3% IQR (0-66.7). SPA did not collect any data for resources in the categories of infrastructure, training or routines. Conclusion: Hospitals in Malawi lack resources for providing emergency and critical care. Increasing data about the availability of resources for emergency and critical care and improving the hospital systems for the care of critically ill patients in Malawi should be prioritized.

Prospective evaluation of diagnostic accuracy of dried blood spots from finger prick samples for determination of HIV-1 load with the NucliSENS Easy-Q HIV-1 version 2.0 assay in Malawi.

HIV-1 viral load (VL) testing is not widely available in resource-limited settings. The use of finger prick dried blood spot (FP-DBS) samples could remove barriers related to sample collection and transport. Measurement of VL using DBS from EDTA venous blood (VB-DBS) in place of plasma has previously been validated using the NucliSENS Easy-Q HIV-1 v2.0 assay, but information on the accuracy of FP-DBS samples for measuring VL is limited. This prospective study, conducted at Thyolo District Hospital in southern Malawi, compared VL levels measured on FP-DBS samples and plasma using the NucliSENS Easy-Q HIV-1 v2.0 assay. Comparability was assessed by means of agreement and correlation (131 patients with VLs of ≥100 copies/ml), sensitivity, and specificity (612 patients on antiretroviral treatment [ART]). Samples of EDTA venous blood and FP-DBS from 1,009 HIV-infected individuals were collected and prepared in the laboratory. Bland-Altman analysis found good agreement between plasma and FP-DBS VL levels, with a mean difference of -0.35 log10, and 95% limits of agreement from -1.26 to 0.55 log10. FP-DBS had a sensitivity of 88.7% (95% confidence interval [CI], 81.1 to 94.4%) and a specificity of 97.8% (95% CI, 96.1 to 98.9%) using a 1,000-copies/ml cut point and a sensitivity of 83.0% (95% CI, 73.4 to 90.1%) and a specificity of 100% (95% CI, 99.3 to 100%) using a 5,000-copies/ml cut point. This study shows that FP-DBS is an acceptable alternative to plasma for measuring VL using the NucliSENS Easy-Q HIV-1 v2.0. We are conducting a second study to assess the proficiency of health workers at preparing FP-DBS in primary health care clinics.

Neurologic manifestations associated with an outbreak of typhoid fever, Malawi--Mozambique, 2009: an epidemiologic investigation.

BACKGROUND: The bacterium Salmonella enterica serovar Typhi causes typhoid fever, which is typically associated with fever and abdominal pain. An outbreak of typhoid fever in Malawi-Mozambique in 2009 was notable for a high proportion of neurologic illness. OBJECTIVE: Describe neurologic features complicating typhoid fever during an outbreak in Malawi-Mozambique METHODS: Persons meeting a clinical case definition were identified through surveillance, with laboratory confirmation of typhoid by antibody testing or blood/stool culture. We gathered demographic and clinical information, examined patients, and evaluated a subset of patients 11 months after onset. A sample of persons with and without neurologic signs was tested for vitamin B6 and B12 levels and urinary thiocyanate. RESULTS: Between March - November 2009, 303 cases of typhoid fever were identified. Forty (13%) persons had objective neurologic findings, including 14 confirmed by culture/serology; 27 (68%) were hospitalized, and 5 (13%) died. Seventeen (43%) had a constellation of upper motor neuron findings, including hyperreflexia, spasticity, or sustained ankle clonus. Other neurologic features included ataxia (22, 55%), parkinsonism (8, 20%), and tremors (4, 10%). Brain MRI of 3 (ages 5, 7, and 18 years) demonstrated cerebral atrophy but no other abnormalities. Of 13 patients re-evaluated 11 months later, 11 recovered completely, and 2 had persistent hyperreflexia and ataxia. Vitamin B6 levels were markedly low in typhoid fever patients both with and without neurologic signs. CONCLUSIONS: Neurologic signs may complicate typhoid fever, and the diagnosis should be considered in persons with acute febrile neurologic illness in endemic areas.

Consumption of pesticide-treated wheat seed by a rural population in Malawi.

An outbreak of typhoid fever in rural Malawi triggered an investigation by the Malawi Ministry of Health and the Centers for Disease Control and Prevention in July 2009. During the investigation, villagers were directly consuming washed, donated, pesticide-treated wheat seed meant for planting. The objective of this study was to evaluate the potential for pesticide exposure and health risk in the outbreak community. A sample of unwashed (1430 g) and washed (759 g) wheat seed donated for planting, but which would have been directly consumed, was tested for 365 pesticides. Results were compared with each other (percentage change), the US Environmental Protection Agency's (EPA) health guidance values and estimated daily exposures were compared with their Reference dose (RfD). Unwashed and washed seed samples contained, respectively: carboxin, 244 and 57 p.p.m.; pirimiphos methyl, 8.18 and 8.56 p.p.m.; total permethrin, 3.62 and 3.27 p.p.m.; and carbaryl, 0.057 and 0.025 p.p.m.. Percentage change calculations (unwashed to washed) were as follows: carboxin, -76.6%; pirimiphos methyl, +4.6%; total permethrin, -9.7%; and carbaryl -56.1%. Only carboxin and total permethrin concentration among washed seed samples exceeded US EPA health guidance values (285 × and seven times, respectively). Adult estimated exposure scenarios (1 kg seed) exceeded the RfD for carboxin (8 × ) and pirimiphos methyl (12 × ). Adult villagers weighing 70 kg would have to consume 0.123, 0.082, 1.06, and 280 kg of washed seed daily to exceed the RfD for carboxin, pirimiphos methyl, permethrins, and carbaryl, respectively. Carboxin, pirimiphos methyl, permethrins, and carbaryl were detected in both unwashed and washed samples of seed. Carboxin, total permethrin, and carbaryl concentration were partially reduced by washing. Health risks from chronic exposure to carboxin and pirimiphos methyl in these amounts are unclear. The extent of this practice among food insecure communities receiving relief seeds and resultant health impact needs further study.

Multidrug-resistant typhoid fever with neurologic findings on the Malawi-Mozambique border.

BACKGROUND: Salmonella enterica serovar Typhi causes an estimated 22 million cases of typhoid fever and 216 000 deaths annually worldwide. We investigated an outbreak of unexplained febrile illnesses with neurologic findings, determined to be typhoid fever, along the Malawi-Mozambique border. METHODS: The investigation included active surveillance, interviews, examinations of ill and convalescent persons, medical chart reviews, and laboratory testing. Classification as a suspected case required fever and ≥1 other finding (eg, headache or abdominal pain); a probable case required fever and a positive rapid immunoglobulin M antibody test for typhoid (TUBEX TF); a confirmed case required isolation of Salmonella Typhi from blood or stool. Isolates underwent antimicrobial susceptibility testing and subtyping by pulsed-field gel electrophoresis (PFGE). RESULTS: We identified 303 cases from 18 villages with onset during March-November 2009; 214 were suspected, 43 were probable, and 46 were confirmed cases. Forty patients presented with focal neurologic abnormalities, including a constellation of upper motor neuron signs (n = 19), ataxia (n = 22), and parkinsonism (n = 8). Eleven patients died. All 42 isolates tested were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole; 4 were also resistant to nalidixic acid. Thirty-five of 42 isolates were indistinguishable by PFGE. CONCLUSIONS: The unusual neurologic manifestations posed a diagnostic challenge that was resolved through rapid typhoid antibody testing in the field and subsequent blood culture confirmation in the Malawi national reference laboratory. Extending laboratory diagnostic capacity, including blood culture, to populations at risk for typhoid fever in Africa will improve outbreak detection, response, and clinical treatment.