ABSTRACT
BACKGROUND: Streptococcus pneumoniae serotype 3 remains a problem globally. Malawi introduced 13-valent pneumococcal conjugate vaccine (PCV13) in 2011, but there has been no direct protection against serotype 3 carriage. We explored whether vaccine escape by serotype 3 is due to clonal expansion of a lineage with a competitive advantage. METHODS: The distribution of serotype 3 Global Pneumococcal Sequence Clusters (GPSCs) and sequence types (STs) globally was assessed using sequences from the Global Pneumococcal Sequencing Project. Whole-genome sequences of 135 serotype 3 carriage isolates from Blantyre, Malawi (2015-2019) were analyzed. Comparative analysis of the capsule locus, entire genomes, antimicrobial resistance, and phylogenetic reconstructions were undertaken. Opsonophagocytosis was evaluated using serum samples from vaccinated adults and children. RESULTS: Serotype 3 GPSC10-ST700 isolates were most prominent in Malawi. Compared with the prototypical serotype 3 capsular polysaccharide locus sequence, 6 genes are absent, with retention of capsule polysaccharide biosynthesis. This lineage is characterized by increased antimicrobial resistance and lower susceptibility to opsonophagocytic killing. CONCLUSIONS: A serotype 3 variant in Malawi has genotypic and phenotypic characteristics that could enhance vaccine escape and clonal expansion after post-PCV13 introduction. Genomic surveillance among high-burden populations is essential to improve the effectiveness of next-generation pneumococcal vaccines.
Subject(s)
Bacterial Capsules , Phylogeny , Pneumococcal Infections , Pneumococcal Vaccines , Serogroup , Streptococcus pneumoniae , Humans , Pneumococcal Vaccines/immunology , Pneumococcal Vaccines/administration & dosage , Streptococcus pneumoniae/genetics , Streptococcus pneumoniae/immunology , Streptococcus pneumoniae/classification , Pneumococcal Infections/prevention & control , Pneumococcal Infections/microbiology , Pneumococcal Infections/immunology , Bacterial Capsules/immunology , Bacterial Capsules/genetics , Malawi , Adult , Whole Genome Sequencing , Child, Preschool , Child , Vaccines, Conjugate/immunology , Male , Genome, Bacterial , Female , Young Adult , Infant , Genotype , Carrier State/microbiologyABSTRACT
INTRODUCTION: The introduction of PCV13 to the Malawi infant immunization schedule in 2011 has been associated with reduced disease from Streptococcus pneumoniae. Improved understanding of serotypes with high invasive potential can guide future vaccination interventions. We aimed to estimate pneumococcal serotypes associated with acute respiratory infection (ARI) and invasive pneumococcal disease (IPD) in hospitalized children in Blantyre, Malawi. METHODS: We analysed data from healthy children under 5 years in the community in Blantyre and children admitted to Queen Elizabeth Central Hospital with ARI between 2015 and 2018. Nasopharyngeal swabs from children were tested for S. pneumoniae and serotyped by latex agglutination if positive. We analysed culture-positive blood and cerebrospinal fluid samples from admitted children between 2012 and 2018 to identify cases of IPD after the introduction of PCV13. We calculated the age-adjusted odds ratio (OR) of carriage for S. pneumoniae vaccine serotypes (VT) comparing those with ARI to healthy children. We also calculated age-adjusted ORs comparing serotypes causing IPD to carriage in the community with OR > 1 indicating high invasive potential. RESULTS: Serotypes 5 (OR 24.73 [95% CI 7.90-78.56] p < 0.001), 1 (OR 23.38 [95% CI 9.75-56.06] p < 0.001), and 6B (OR 4.73 [95% CI 1.66-11.64] p = 0.001) had high invasive potential. Serotype 6B was no longer significant (OR 1.34 [95% CI 0.07-6.87] p = 0.777) in a sensitivity analysis accounting for year of recruitment. The prevalence of S. pneumoniae carriage in the community was 72.6% [95% CI 71.3-74.0] (3078/4238) and 23.4% (719/3078) of positive community samples were VT. The carriage prevalence in those hospitalised with ARI was 45.5% [95% CI 42.1-48.9] (389/855) and 43.8% of hospital attendees reported antibiotic use prior to admission. We did not identify significant associations with carriage of any serotypes in those with ARI. CONCLUSIONS: Pneumococcal serotypes 5 and 1 are associated with high invasive potential. Despite high community pneumococcal carriage, pre-hospital antibiotic usage likely reduces pneumococcal detection among children admitted in this setting and further research is needed to investigate serotypes associated with ARI. Data from this study can guide future preventative vaccination strategies in Malawi.
Subject(s)
Pneumococcal Infections , Respiratory Tract Infections , Infant , Child , Humans , Child, Preschool , Serogroup , Malawi/epidemiology , Carrier State/epidemiology , Nasopharynx , Streptococcus pneumoniae , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines , Anti-Bacterial AgentsABSTRACT
BACKGROUND: Hepatitis B is the leading cause of cirrhosis and liver cancer in sub-Saharan Africa. To reduce mortality, antiviral treatment programs are needed. We estimated prevalence, vaccine impact, and need for antiviral treatment in Blantyre, Malawi. METHODS: We conducted a household study in 2016-2018. We selected individuals from a census using random sampling and estimated age-sex-standardized hepatitis B surface antigen (HBsAg) seroprevalence. Impact of infant hepatitis B vaccination was estimated by binomial log-linear regression comparing individuals born before and after vaccine implementation. In HBsAg-positive adults, eligibility for antiviral therapy was assessed. RESULTS: Of 97386 censused individuals, 6073 (median age 18 years; 56.7% female) were sampled. HBsAg seroprevalence was 5.1% (95% confidence interval [CI], 4.3%-6.1%) among adults and 0.3% (95% CI, .1%-.6%) among children born after vaccine introduction. Estimated vaccine impact was 95.8% (95% CI, 70.3%-99.4%). Of HBsAg-positive adults, 26% were HIV-positive. Among HIV-negative individuals, 3%, 6%, and 9% were eligible for hepatitis B treatment by WHO, European, and American hepatology association criteria, respectively. CONCLUSIONS: Infant HBV vaccination has been highly effective in reducing HBsAg prevalence in urban Malawi. Up to 9% of HBsAg-positive HIV-negative adults are eligible, but have an unmet need, for antiviral therapy.
Subject(s)
HIV Infections , Hepatitis B , Adolescent , Adult , Antiviral Agents/therapeutic use , Child , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , Hepatitis B/drug therapy , Hepatitis B/epidemiology , Hepatitis B/prevention & control , Hepatitis B Surface Antigens , Hepatitis B Vaccines/therapeutic use , Hepatitis B virus , Humans , Infant , Malawi/epidemiology , Male , Seroepidemiologic Studies , VaccinationABSTRACT
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.
Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Blood Donors , COVID-19 Vaccines , Cross-Sectional Studies , Humans , Pandemics , Seroepidemiologic StudiesABSTRACT
Accurate assessment of the serotype distribution associated with pneumococcal colonization and disease is essential for evaluating and formulating pneumococcal vaccines and for informing vaccine policy. For this reason, we evaluated the concordance between pneumococcal serotyping results by latex agglutination, whole-genome sequencing (WGS) with PneumoCaT, and DNA microarray for samples from community carriage surveillance in Blantyre, Malawi. Nasopharyngeal swabs were collected according to WHO recommendations between 2015 and 2017 by using stratified random sampling among study populations. Participants included healthy children 3 to 6 years old (vaccinated with the 13-valent pneumococcal conjugate vaccine [PCV13] as part of the Expanded Program on Immunization [EPI]), healthy children 5 to 10 years old (age-ineligible for PCV13), and HIV-infected adults (18 to 40 years old) on antiretroviral therapy (ART). For phenotypic serotyping, we used a 13-valent latex kit (Statens Serum Institut [SSI], Denmark). For genomic serotyping, we applied the PneumoCaT pipeline to whole-genome sequence libraries. For molecular serotyping by microarray, we used the BUGS Bioscience Senti-SP microarray. A total of 1,347 samples were analyzed. Concordance was 90.7% (95% confidence interval [CI], 89.0 to 92.2%) between latex agglutination and PneumoCaT, 95.2% (95% CI, 93.9 to 96.3%) between latex agglutination and the microarray, and 96.6% (95% CI, 95.5 to 97.5%) between the microarray and PneumoCaT. By detecting additional vaccine serotype (VT) pneumococci carried at low relative abundances (median, 8%), the microarray increased VT detection by 31.5% over that by latex serotyping. To conclude, all three serotyping methods were highly concordant in identifying dominant serotypes. Latex serotyping is accurate in identifying vaccine serotypes and requires the least expertise and resources for field implementation and analysis. However, WGS, which adds population structure, and microarray, which adds multiple-serotype carriage, should be considered at regional reference laboratories for investigating the importance of vaccine serotypes at low relative abundances in transmission and disease.
Subject(s)
Latex Fixation Tests , Pneumococcal Infections , Adolescent , Adult , Carrier State/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Humans , Infant , Malawi/epidemiology , Nasopharynx , Oligonucleotide Array Sequence Analysis , Pneumococcal Vaccines , Prevalence , Serotyping , Young AdultABSTRACT
BACKGROUND: Globally, Médecins Sans Frontières (MSF) treats more than 300,000 severely malnourished children annually. Malnutrition is not only caused by lack of food and poor infant and child feeding practices but also by illnesses. Breaking the vicious cycle of illness and malnutrition by providing ill children with nutritional supplementation is a potentially powerful strategy for preventing malnutrition that has not been adequately investigated. Therefore, MSF investigated whether incidence of malnutrition among ill children <5 y old could be reduced by providing a fortified food product or micronutrients during their 2-wk convalescence period. Two trials, one in Nigeria and one in Uganda, were conducted; here we report on the trial that took place in Goronyo, a rural region of northwest Nigeria with high morbidity and malnutrition rates. METHODS AND FINDINGS: We investigated the effect of supplementation with ready-to-use therapeutic food (RUTF) and a micronutrient powder (MNP) on the incidence of malnutrition in ill children presenting at an outpatient clinic in Goronyo during February to September 2012. A three-armed, partially-blinded, randomised controlled trial was conducted in children diagnosed as having malaria, diarrhoea, or lower respiratory tract infection. Children aged 6 to 59 mo were randomised to one of three arms: one sachet/d of RUTF; two sachets/d of micronutrients or no supplement (control) for 14 d for each illness over 6 mo. The primary outcome was the incidence of first negative nutritional outcome (NNO) during the 6 mo follow-up. NNO was a study-specific measure used to indicate occurrence of malnutrition; it was defined as low weight-for-height z-score (<-2 for non-malnourished and <-3 for moderately malnourished children), mid-upper arm circumference <115 mm, or oedema, whichever came first. Of the 2,213 randomised participants, 50.0% were female and the mean age was 20.2 (standard deviation 11.2) months; 160 (7.2%) were lost to follow-up, 54 (2.4%) were admitted to hospital, and 29 (1.3%) died. The incidence rates of NNO for the RUTF, MNP, and control groups were 0.522 (95% confidence interval (95% CI), 0.442-0.617), 0.495 (0.415-0.589), and 0.566 (0.479-0.668) first events/y, respectively. The incidence rate ratio was 0.92 (95% CI, 0.74-1.15; p = 0.471) for RUTF versus control; 0.87 (0.70-1.10; p = 0.242) for MNP versus control and 1.06 (0.84-1.33, p = 0.642) for RUTF versus MNP. A subgroup analysis showed no interaction nor confounding, nor a different effectiveness of supplementation, among children who were moderately malnourished compared with non-malnourished at enrollment. The average number of study illnesses for the RUTF, MNP, and control groups were 4.2 (95% CI, 4.0-4.3), 3.4 (3.2-3.6), and 3.6 (3.4-3.7). The proportion of children who died in the RUTF, MNP, and control groups were 0.8% (95% CI, 0.3-1.8), 1.8% (1.0-3.3), and 1.4% (0.7-2.8). CONCLUSIONS: A 2-wk supplementation with RUTF or MNP to ill children as part of routine primary medical care did not reduce the incidence of malnutrition. The lack of effect in Goronyo may be due to a high frequency of morbidity, which probably further affects a child's nutritional status and children's ability to escape from the illness-malnutrition cycle. The duration of the supplementation may have been too short or the doses of the supplements may have been too low to mitigate the effects of high morbidity and pre-existing malnutrition. An integrated approach combining prevention and treatment of diseases and treatment of moderate malnutrition, rather than prevention of malnutrition by nutritional supplementation alone, might be more effective in reducing the incidence of acute malnutrition in ill children. TRIAL REGISTRATION: clinicaltrials.gov NCT01154803.
Subject(s)
Dietary Supplements , Food, Fortified , Malnutrition/prevention & control , Micronutrients/administration & dosage , Child, Preschool , Chronic Disease , Female , Follow-Up Studies , Humans , Incidence , Infant , Male , Malnutrition/epidemiology , Malnutrition/etiology , Nigeria/epidemiology , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Globally, Médecins Sans Frontières (MSF) treats more than 300,000 severely malnourished children annually. Malnutrition is not only caused by lack of food but also by illnesses and by poor infant and child feeding practices. Breaking the vicious cycle of illness and malnutrition by providing ill children with nutritional supplementation is a potentially powerful strategy for preventing malnutrition that has not been adequately investigated. Therefore, MSF investigated whether incidence of malnutrition among ill children <5 y old could be reduced by providing a fortified food product or micronutrients during their 2-wk convalescence period. Two trials, one in Nigeria and one in Uganda, were conducted; here, we report on the trial that took place in Kaabong, a poor agropastoral region of Karamoja, in east Uganda. While the region of Karamoja shows an acute malnutrition rate between 8.4% and 11.5% of which 2% to 3% severe malnutrition, more than half (58%) of the population in the district of Kaabong is considered food insecure. METHODS AND FINDINGS: We investigated the effect of two types of nutritional supplementation on the incidence of malnutrition in ill children presenting at outpatient clinics during March 2011 to April 2012 in Kaabong, Karamoja region, Uganda, a resource-poor region where malnutrition is a chronic problem for its seminomadic population. A three-armed, partially-blinded, randomised controlled trial was conducted in children diagnosed with malaria, diarrhoea, or lower respiratory tract infection. Non-malnourished children aged 6 to 59 mo were randomised to one of three arms: one sachet/d of ready-to-use therapeutic food (RUTF), two sachets/d of micronutrient powder (MNP), or no supplement (control) for 14 d for each illness over 6 mo. The primary outcome was the incidence of first negative nutritional outcome (NNO) during the 6 mo follow-up. NNO was a study-specific measure used to indicate progression to moderate or severe acute malnutrition; it was defined as weight-for-height z-score <-2, mid-upper arm circumference (MUAC) <115 mm, or oedema, whichever came first. Of the 2,202 randomised participants, 51.2% were girls, and the mean age was 25.2 (±13.8) mo; 148 (6.7%) participants were lost to follow-up, 9 (0.4%) died, and 14 (0.6%) were admitted to hospital. The incidence rates of NNO (first event/year) for the RUTF, MNP, and control groups were 0.143 (95% confidence interval [CI], 0.107-0.191), 0.185 (0.141-0.239), and 0.213 (0.167-0.272), respectively. The incidence rate ratio was 0.67 (95% CI, 0.46-0.98; p = 0.037) for RUTF versus control; a reduction of 33.3%. The incidence rate ratio was 0.86 (0.61-1.23; p = 0.413) for MNP versus control and 0.77 for RUTF versus MNP (95% CI 0.52-1.15; p = 0.200). The average numbers of study illnesses for the RUTF, MNP, and control groups were 2.3 (95% CI, 2.2-2.4), 2.1 (2.0-2.3), and 2.3 (2.2-2.5). The proportions of children who died in the RUTF, MNP, and control groups were 0%, 0.8%, and 0.4%. The findings apply to ill but not malnourished children and cannot be generalised to a general population including children who are not necessarily ill or who are already malnourished. CONCLUSIONS: A 2-wk nutrition supplementation programme with RUTF as part of routine primary medical care to non-malnourished children with malaria, LRTI, or diarrhoea proved effective in preventing malnutrition in eastern Uganda. The low incidence of malnutrition in this population may warrant a more targeted intervention to improve cost effectiveness. TRIAL REGISTRATION: clinicaltrials.gov NCT01497236.
Subject(s)
Dietary Supplements , Malnutrition/prevention & control , Micronutrients/administration & dosage , Body Weight , Child, Preschool , Chronic Disease , Female , Follow-Up Studies , Humans , Incidence , Infant , Male , Malnutrition/epidemiology , Malnutrition/etiology , Time Factors , Treatment Outcome , Uganda/epidemiologyABSTRACT
Since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Malawi in 2011, there has been persistent carriage of vaccine serotype (VT) Streptococcus pneumoniae, despite high vaccine coverage. To determine if there has been a genetic change within the VT capsule polysaccharide (cps) loci since the vaccine's introduction, we compared 1022 whole-genome-sequenced VT isolates from 1998 to 2019. We identified the clonal expansion of a multidrug-resistant, penicillin non-susceptible serotype 23F GPSC14-ST2059 lineage, a serotype 14 GPSC9-ST782 lineage and a novel serotype 14 sequence type GPSC9-ST18728 lineage. Serotype 23F GPSC14-ST2059 had an I253T mutation within the capsule oligosaccharide repeat unit polymerase Wzy protein, which is predicted in silico to alter the protein pocket cavity. Moreover, serotype 23F GPSC14-ST2059 had SNPs in the DNA binding sites for the cps transcriptional repressors CspR and SpxR. Serotype 14 GPSC9-ST782 harbours a non-truncated version of the large repetitive protein (Lrp), containing a Cna protein B-type domain which is also present in proteins associated with infection and colonisation. These emergent lineages also harboured genes associated with antibiotic resistance, and the promotion of colonisation and infection which were absent in other lineages of the same serotype. Together these data suggest that in addition to serotype replacement, modifications of the capsule locus associated with changes in virulence factor expression and antibiotic resistance may promote vaccine escape. In summary, the study highlights that the persistence of vaccine serotype carriage despite high vaccine coverage in Malawi may be partly caused by expansion of VT lineages post-PCV13 rollout.
Subject(s)
Bacterial Capsules , Pneumococcal Infections , Pneumococcal Vaccines , Serogroup , Streptococcus pneumoniae , Streptococcus pneumoniae/genetics , Streptococcus pneumoniae/classification , Streptococcus pneumoniae/pathogenicity , Pneumococcal Vaccines/immunology , Humans , Malawi , Bacterial Capsules/genetics , Pneumococcal Infections/microbiology , Pneumococcal Infections/prevention & control , Vaccines, Conjugate , Polysaccharides, Bacterial/genetics , Polysaccharides, Bacterial/immunology , Virulence/genetics , Genotype , Whole Genome Sequencing , Bacterial Proteins/genetics , Virulence Factors/genetics , Child, Preschool , Polymorphism, Single Nucleotide , Infant , MaleABSTRACT
INTRODUCTION: Vaccination is a potentially critical component of efforts to arrest development and dissemination of antimicrobial resistance (AMR), though little is known about vaccination impact within low-income and middle-income countries. This study will evaluate the impact of vaccination on reducing carriage prevalence of resistant Streptococcus pneumoniae and extended spectrum beta-lactamase-producing Escherichia coli and Klebsiella species. We will leverage two large ongoing cluster-randomised vaccine evaluations in Malawi assessing; first, adding a booster dose to the 13-valent pneumococcal conjugate vaccine (PCV13) schedule, and second, introduction of the RTS,S/AS01 malaria vaccine. METHODS AND ANALYSIS: Six cross-sectional surveys will be implemented within primary healthcare centres (n=3000 users of outpatient facilities per survey) and their local communities (n=700 healthy children per survey): three surveys in Blantyre district (PCV13 component) and three surveys in Mangochi district (RTS,S/AS01 component). We will evaluate antibiotic prescription practices and AMR carriage in children ≤3 years. For the PCV13 component, surveys will be conducted 9, 18 and 33 months following a 3+0 to 2+1 schedule change. For the RTS,S/AS01 component, surveys will be conducted 32, 44 and 56 months post-RTS,S/AS01 introduction. Six health centres in each study component will be randomly selected for study inclusion. Between intervention arms, the primary outcome will be the difference in penicillin non-susceptibility prevalence among S. pneumoniae nasopharyngeal carriage isolates in healthy children. The study is powered to detect an absolute change of 13 percentage points (ie, 35% vs 22% penicillin non-susceptibility). ETHICS AND DISSEMINATION: This study has been approved by the Kamuzu University of Health Sciences (Ref: P01-21-3249), University College London (Ref: 18331/002) and University of Liverpool (Ref: 9908) Research Ethics Committees. Parental/caregiver verbal or written informed consent will be obtained prior to inclusion or recruitment in the health centre-based and community-based activities, respectively. Results will be disseminated via the Malawi Ministry of Health, WHO, peer-reviewed publications and conference presentations.
Subject(s)
Malaria Vaccines , Malaria , Pneumococcal Infections , Humans , Child , Infant , Child, Preschool , Streptococcus pneumoniae , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cross-Sectional Studies , Malawi/epidemiology , Drug Resistance, Bacterial , Pneumococcal Vaccines , Vaccination , Penicillins , Nasopharynx , Malaria/epidemiology , Malaria/prevention & control , Carrier State/epidemiologyABSTRACT
Streptococcus pneumoniae causes substantial mortality among children under 5-years-old worldwide. Polysaccharide conjugate vaccines (PCVs) are highly effective at reducing vaccine serotype disease, but emergence of non-vaccine serotypes and persistent nasopharyngeal carriage threaten this success. We investigated the hypothesis that following vaccine, adapted pneumococcal genotypes emerge with the potential for vaccine escape. We genome sequenced 2804 penumococcal isolates, collected 4-8 years after introduction of PCV13 in Blantyre, Malawi. We developed a pipeline to cluster the pneumococcal population based on metabolic core genes into "Metabolic genotypes" (MTs). We show that S. pneumoniae population genetics are characterised by emergence of MTs with distinct virulence and antimicrobial resistance (AMR) profiles. Preliminary in vitro and murine experiments revealed that representative isolates from emerging MTs differed in growth, haemolytic, epithelial infection, and murine colonisation characteristics. Our results suggest that in the context of PCV13 introduction, pneumococcal population dynamics had shifted, a phenomenon that could further undermine vaccine control and promote spread of AMR.
Subject(s)
Pneumococcal Infections , Streptococcus pneumoniae , Child , Humans , Animals , Mice , Infant , Child, Preschool , Streptococcus pneumoniae/genetics , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Malawi/epidemiology , Virulence/genetics , Drug Resistance, Bacterial/genetics , Pneumococcal Vaccines , Serogroup , Nasopharynx , Carrier State/epidemiologyABSTRACT
Invasive pneumococcal disease (IPD) risk increases with age for older adults whereas the population size benefiting from pneumococcal vaccines and robustness of immunogenic response to vaccination decline. We estimate how demographics, vaccine efficacy/effectiveness (VE), and waning VE impact on optimal age for a single-dose pneumococcal vaccination. Age- and vaccine-serotype-specific IPD cases from routine surveillance of adults ≥ 55 years old (y), ≥ 4-years after infant-pneumococcal vaccine introduction and before 2020, and VE data from prior studies were used to estimate IPD incidence and waning VE which were then combined in a cohort model of vaccine impact. In Brazil, Malawi, South Africa and England 51, 51, 54 and 39% of adults older than 55 y were younger than 65 years old, with a smaller share of annual IPD cases reported among < 65 years old in England (4,657; 20%) than Brazil (186; 45%), Malawi (4; 63%), or South Africa (134, 48%). Vaccination at 55 years in Brazil, Malawi, and South Africa, and at 70 years in England had the greatest potential for IPD prevention. Here, we show that in low/middle-income countries, pneumococcal vaccines may prevent a substantial proportion of residual IPD burden if administered earlier in adulthood than is typical in high-income countries.
Subject(s)
Pneumococcal Infections , Infant , Humans , Aged , Middle Aged , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines , Vaccination , Serogroup , IncidenceABSTRACT
The SARS-CoV-2 Omicron variant has resulted in a high number of cases, but a relatively low incidence of severe disease and deaths, compared to the pre-Omicron variants. Therefore, we assessed the differences in symptom prevalence between Omicron and pre-Omicron infections in a sub-Saharan African population. We collected data from outpatients presenting at two primary healthcare facilities in Blantyre, Malawi, from November 2020 to March 2022. Eligible participants were aged >1month old, with signs suggestive of COVID-19, and those not suspected of COVID-19, from whom we collected nasopharyngeal swabs for SARS-CoV-2 PCR testing, and sequenced positive samples to identify infecting-variants. In addition, we calculated the risk of presenting with a given symptom in individuals testing SARS-CoV-2 PCR positive before and during the Omicron variant-dominated period. Among 5176 participants, 6.4% were under 5, and 77% were aged 18 to 50 years. SARS-CoV-2 infection prevalence peaked in January 2021 (Beta), July 2021 (Delta), and December 2021 (Omicron). We found that cough (risk ratio (RR), 1.50; 95% confidence interval (CI), 1.00 to 2.30), fatigue (RR 2.27; 95% CI, 1.29 to 3.86) and headache (RR 1.64; 95% CI, 1.15 to 2.34) were associated with a high risk of SARS-CoV-2 infection during the pre-Omicron period. In comparison, only headache (RR 1.41; 95% CI, 1.07 to 1.86) did associate with a high risk of SARS-CoV-2 infection during the Omicron-dominated period. In conclusion, clinical symptoms associated with Omicron infection differed from prior variants and were harder to identify clinically with current symptom guidelines. Our findings encourage regular review of case definitions and testing policies to ensure case ascertainment.
ABSTRACT
Background: The B.1.1.529 (Omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the fourth COVID-19 pandemic wave across the southern African region, including Malawi. The seroprevalence of SARS-CoV-2 antibodies and their association with epidemiological trends of hospitalisations and deaths are needed to aid locally relevant public health policy decisions. Methods: We conducted a population-based serosurvey from December 27, 2021 to January 17, 2022, in 7 districts across Malawi to determine the seroprevalence of SARS-CoV-2 antibodies. Serum samples were tested for antibodies against SARS-CoV-2 receptor binding domain using WANTAI SARS-CoV-2 Receptor Binding Domain total antibody commercial enzyme-linked immunosorbent assay (ELISA). We also evaluated COVID-19 epidemiologic trends in Malawi, including cases, hospitalisations and deaths from April 1, 2021 through April 30, 2022, collected using the routine national COVID-19 reporting system. A multivariable logistic regression model was developed to investigate the factors associated with SARS-CoV-2 seropositivity. Findings: Serum samples were analysed from 4619 participants (57% female; 60% aged 18-50 years), of whom 878/3794 (23%) of vaccine eligible adults had received a single dose of any COVID-19 vaccine. The overall assay-adjusted seroprevalence was 83.7% (95% confidence interval (CI), 79.3%-93.4%). Seroprevalence was lowest among children <13 years of age (66%) and highest among adults 18-50 years of age (82%). Seroprevalence was higher among vaccinated compared to unvaccinated participants (1 dose, 94% vs. 77%, adjusted odds ratio 4.89 [95% CI, 3.43-7.22]; 2 doses, 97% vs. 77%, aOR 6.62 [95% CI, 4.14-11.3]). Urban residents were more likely to be seropositive than those from rural settings (91% vs. 78%, aOR 2.76 [95% CI, 2.16-3.55]). There was at least a two-fold reduction in the proportion of hospitalisations and deaths among the reported cases in the fourth wave compared to the third wave (hospitalisations, 10.7% (95% CI, 10.2-11.3) vs. 4.86% (95% CI, 4.52-5.23), p < 0.0001; deaths, 3.48% (95% CI, 3.18-3.81) vs. 1.15% (95% CI, 1.00-1.34), p < 0.0001). Interpretation: We report reduction in proportion of hospitalisations and deaths from SARS-CoV-2 infections during the Omicron variant dominated wave in Malawi, in the context of high SARS-CoV-2 seroprevalence and low COVID-19 vaccination coverage. These findings suggest that COVID-19 vaccination policy in high seroprevalence settings may need to be amended from mass campaigns to targeted vaccination of reported at-risk populations. Funding: Supported by the Bill and Melinda Gates Foundation (INV-039481).
ABSTRACT
OBJECTIVE: Adults living with HIV (ALWHIV) on antiretroviral therapy (ART) are at high risk of pneumococcal carriage and disease. To help evaluate carriage risk in African ALWHIV at least 4 years after infant pneumococcal conjugate vaccination introduction in 2011, we assessed association between pneumococcal carriage and potential risk factors. METHODS: Nasopharyngeal swabs were collected from adults aged 18-40âyears attending an ART clinic during rolling, cross-sectional surveys in Blantyre, Malawi between 2015 and 2019. We fitted generalized additive models to estimate the risk of sex, social economic status (SES), living with a child less than 5 years, and ART duration on carriage. RESULTS: Of 2067 adults, median age was 33 years (range 28-37), 1427 (69.0%) were women, 1087 (61.4%) were in low-middle socioeconomic-status (SES), 910 (44.0%) were living with a child less than 5 years, and median ART duration was 3âyears (range 0.004-17). We estimated 38.2 and 60.6% reductions in overall and vaccine-serotype carriage prevalence. Overall carriage was associated with low SES, living with a child less than 5 years and shorter duration on ART. By contrast, vaccine-type carriage was associated with living without a child less than 5 years and male sex. CONCLUSION: Despite temporal reductions in overall and vaccine-serotype carriage, there is evidence of incomplete vaccine-serotype indirect protection. A targeted-vaccination campaign should be considered for ALWHIV, along with other public health measures to further reduce vaccine-serotype carriage and therefore disease.
Subject(s)
HIV Infections , Pneumococcal Infections , Adult , Female , Humans , Infant , Male , Carrier State/epidemiology , Cross-Sectional Studies , HIV Infections/complications , HIV Infections/drug therapy , Malawi/epidemiology , Nasopharynx , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines , Prevalence , Risk Factors , Streptococcus pneumoniae , Infant, Newborn , Child, PreschoolABSTRACT
BACKGROUND: Invasive pneumococcal disease (IPD) in young infants is uncommon but associated with high morbidity and mortality. Accurate data on the burden of IPD in young infants in low-income countries are lacking. We examined the burden of IPD in infants <90 days old in Blantyre, Malawi over a 14-year period and evaluated the indirect impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on vaccine-serotype IPD (VT-IPD) in this population. METHODS: We conducted laboratory-based prospective IPD surveillance in infants <90 days of age admitted to Queen Elizabeth Central Hospital in Blantyre between 2005 and 2018, including 7 years pre-PCV13 and 7 years post-PCV13 introduction. IPD was defined as Streptococcus pneumoniae identified by culture from blood or cerebrospinal fluid. Serotypes were determined by multiplex polymerase chain reaction and latex agglutination testing. RESULTS: We identified 130 cases of culture-confirmed IPD in infants <90 days old between 2005 and 2018. Total IPD incidence was declining before PCV13 introduction. The mean incidence of IPD was significantly lower in the post-PCV13 era. Serotypes 5 (27.8%) and 1 (15.6%) were most prevalent. Even after PCV13 introduction, VTs remained the primary cause of IPD, with serotype 5 accounting for 17.4% and serotype 1 for 13.0% of cases in young infants. CONCLUSION: Vaccine serotypes 1 and 5 were the main cause of IPD in neonates and young infants, both before and after PCV13 introduction. This suggests incomplete indirect protection with persisting VT carriage across the population despite vaccination in this setting. Alternative vaccine schedules and other vaccine introduction approaches need to be considered to protect this vulnerable population.
Subject(s)
Pneumococcal Infections , Pneumococcal Vaccines , Hospitals , Humans , Incidence , Infant , Infant, Newborn , Malawi/epidemiology , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Prospective Studies , Serogroup , Vaccines, ConjugateABSTRACT
BACKGROUND: Household air pollution from solid fuels increases the risk of childhood pneumonia. Nasopharyngeal carriage of Streptococcus pneumoniae is a necessary step in the development of pneumococcal pneumonia. We aimed to assess the association between exposure to household air pollution and the prevalence and density of S pneumoniae carriage among children. METHODS: The Malawi Streptococcus pneumoniae Carriage and Air Pollution Exposure study was a nested, prospective, observational study of children participating in the cluster randomised controlled Cooking and Pneumonia Study (CAPS) in the Karonga Health and Demographic Surveillance System (HDSS) area in northern Malawi. CAPS compared the effects of a cleaner burning biomass-fuelled cookstove (intervention group) with traditional open-fire cooking (control group) on the incidence of pneumonia in children. Eligible children aged 6 weeks or 6 months (those recruited a 6 weeks were also followed up at age 6 months) were identified by the Karonga HDSS centre. Nasopharyngeal swabs were taken to detect S pneumoniae, and infant exposure to particulate matter with a diameter of ≤2·5 µm (PM2·5) exposure was assessed by use of a MicroPEM device. The primary outcome was the prevalence of nasopharyngeal S pneumoniae carriage in all children aged 6 months, assessed in all children with valid data on PM2·5. The effects of the intervention stoves (intention-to-treat analysis) and PM2·5 (adjusted exposure-response analysis) on the prevalence of S pneumoniae carriage were also assessed in the study children. FINDINGS: Between Nov 15, 2015, and Nov 2, 2017, 485 children were recruited (240 from the intervention group and 245 from the control group). Of all 450 children with available data at age 6 months, 387 (86% [95% CI 82-89]) were positive for S pneumoniae. Geometric mean PM2·5 exposure was 60·3 µg/m3 (95% CI 55·8-65·3) in S pneumoniae-positive children and 47·0 µg/m3 (38·3-57·7) in S pneumoniae-negative children (p=0·044). In the intention-to-treat analysis, a non-significant increase in the risk of S pneumoniae carriage was observed in intervention group children compared with control group children (odds ratio 1·36 [95% CI 0·95-1·94]; p=0·093). In the exposure-response analysis, a significant association between PM2·5 exposure and S pneumoniae carriage was observed; a one unit increase in decile of PM2·5 was found to significantly increase the risk of S pneumoniae carriage by 10% (1·10 [1·01-1·20]; p=0·035), after adjustment for age, sex, 13-valent pneumococcal conjugate vaccination status, season, current use of antibiotics, and MicroPEM run-time. INTERPRETATION: Despite the absence of effect from the intervention cookstove, household air pollution exposure was significantly associated with the prevalence of nasopharyngeal S pneumoniae carriage. These results provide empirical evidence for the potential mechanistic association between exposure to household air pollution and childhood pneumonia. FUNDING: Bill & Melinda Gates Foundation.
Subject(s)
Air Pollution, Indoor/statistics & numerical data , Carrier State/epidemiology , Cooking/methods , Pneumococcal Infections/epidemiology , Female , Humans , Infant , Malawi/epidemiology , Male , Nasopharynx/microbiology , Prospective Studies , Streptococcus pneumoniae/isolation & purificationABSTRACT
BACKGROUND: Pneumococcal conjugate vaccines (PCVs) induce serotype-specific IgG antibodies, effectively reducing vaccine-serotype carriage and invasive pneumococcal disease (IPD). IgG production wanes approximately 1 month after vaccination in absence of serotype-specific exposure. With uncertainty surrrounding correlate of protection (CoP) estimates and with persistent vaccine-serotype carriage and vaccine-serotype IPD after PCV13 introduction, we aimed to profile population-level immunogenicity among children younger than 5 years in Blantyre, Malawi. METHODS: For this serosurveillance study, we used a random subset of samples from a prospective population-based serosurvey in Blantyre, Malawi, done between Dec 16, 2016, and June 27, 2018. Sample selection was based on age category optimisation among children younger than 5 years, adequate sample volume, and available budget. We measured serotype-specific IgGs against the 13 vaccine serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) and two non-vaccine serotypes (12F and 33F), as well as IgGs against three pneumococcal proteins (PsaA, NanA, and Ply), using ELISA and a direct-binding electrochemiluminescence-based multiplex assay. We estimated population-level, serotype-specific immunogenicity profiles using a linear spline regression model. Analyses included samples stratified to 20 3-month age strata (eg, age <3 months to 57-59 months). FINDINGS: We evaluated 638 plasma samples: 556 primary samples and 82 unique secondary samples (each linked to one primary sample). Immunogenicity profiles revealed a consistent pattern among vaccine serotypes except serotype 3: a vaccine-induced IgG peak followed by waning to a nadir and subsequent increase in titre. For serotype 3, we observed no apparent vaccine-induced increase. Heterogeneity in parameters included age range at post-vaccination nadir (from 11·2 months [19A] to 27·3 months [7F]). The age at peak IgG titre ranged from 2·69 months (5) to 6·64 months (14). Titres dropped below CoPs against IPD among nine vaccine serotypes (1, 3, 4, 5, 6B, 7F, 9V, 18C, and 23F) and below CoPs against carriage for ten vaccine serotypes (1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F). Increasing antibody concentrations among older children and seroincident events were consistent with ongoing vaccine-serotype exposure. INTERPRETATION: A 3â+â0 PCV13 schedule with high uptake has not led to sustained population-level antibody immunity beyond the first year of life. Indeed, post-vaccine antibody concentrations dropped below putative CoPs for several vaccine serotypes, potentially contributing to persistent vaccine-serotype carriage and residual vaccine-serotype IPD in Malawi and other similar settings. Policy decisions should consider alternative vaccine strategies, including a booster dose, to achieve sustained vaccine-induced antibody titres, and thus control. FUNDING: Bill & Melinda Gates Foundation, Wellcome UK, and National Institute for Health and Care Research.
Subject(s)
Antibodies, Bacterial , Pneumococcal Infections , Child , Humans , Infant , Adolescent , Child, Preschool , Vaccines, Conjugate , Malawi/epidemiology , Prospective Studies , Pneumococcal Vaccines , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Immunoglobulin GABSTRACT
Childhood pneumococcal conjugate vaccine (PCV) protects against invasive pneumococcal disease caused by vaccine-serotype (VT) Streptococcus pneumoniae by generating opsonophagocytic anti-capsular antibodies, but how vaccination protects against and reduces VT carriage is less well understood. Using serological samples from PCV-vaccinated Malawian individuals and a UK human challenge model, we explored whether antibody quality (IgG subclass, opsonophagocytic killing, and avidity) is associated with protection from carriage. Following experimental challenge of adults with S. pneumoniae serotype 6B, 3/21 PCV13-vaccinees were colonised with pneumococcus compared to 12/24 hepatitis A-vaccinated controls; PCV13-vaccination induced serotype-specific IgG, IgG1, and IgG2, and strong opsonophagocytic responses. However, there was no clear relationship between antibody quality and protection from carriage or carriage intensity after vaccination. Similarly, among PCV13-vaccinated Malawian infants there was no relationship between serotype-specific antibody titre or quality and carriage through exposure to circulating serotypes. Although opsonophagocytic responses were low in infants, antibody titre and avidity to circulating serotypes 19F and 6A were maintained or increased with age. These data suggest a complex relationship between antibody-mediated immunity and pneumococcal carriage, and that PCV13-driven antibody quality may mature with age and exposure.
Subject(s)
Pneumococcal Infections , Streptococcus pneumoniae , Humans , Child , Infant , Adult , Child, Preschool , Antibody Formation , Pneumococcal Vaccines , Pneumococcal Infections/prevention & control , Vaccines, Conjugate , Vaccination , Immunoglobulin G , NasopharynxABSTRACT
Posttraumatic stress disorder (PTSD) symptoms, exposure to traumatic stressors, and health care utilization were examined in 84 women attending a primary health care clinic in Mogadishu, Somalia. The Somalia-Posttraumatic Diagnostic Scale was used in this active warzone to measure symptoms. Nearly all women reported high levels of confrontations with violence; half described being exposed to a potentially traumatizing event. Nearly one third had significant PTSD symptoms. Compared to those who did not, women who reported exposure to a traumatic stressor reported more confrontations with violence (7.1 vs. 3.3; p < . 001), health complaints (3.8 vs. 2.9; p = .03), and nearly 3 times as much (p = .03) health service utilization. A potentially traumatizing event was found to be a simplified proxy for assessing mental health distress in women attending a primary health care facility in highly insecure, unpredictable, resource-limited settings.
Subject(s)
Stress Disorders, Post-Traumatic/physiopathology , Violence/psychology , Adolescent , Adult , Female , Humans , Interviews as Topic , Middle Aged , Severity of Illness Index , Somalia/epidemiology , Stress Disorders, Post-Traumatic/epidemiology , Young AdultABSTRACT
Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and bacteremia. Serotype 1 is rarely carried but is commonly associated with invasive pneumococcal disease, and in the African "meningitis belt," it is prone to cause cyclical epidemics. We report the complete genome sequence of S. pneumoniae serotype 1 strain BVJ1JL, isolated in Malawi.