Genomic Microevolution of Vibrio cholerae O1, Lake Tanganyika Basin, Africa.

Africa's Lake Tanganyika basin is a cholera hotspot. During 2001-2020, Vibrio cholerae O1 isolates obtained from the Democratic Republic of the Congo side of the lake belonged to 2 of the 5 clades of the AFR10 sublineage. One clade became predominant after acquiring a parC mutation that decreased susceptibility to ciprofloxacin.

Evaluating lactate prognostic value in children suspected of acetaminophen-induced liver failure in Liberia.

BACKGROUND: The prognostic significance of hyperlactatemia in young children with liver injury suspected to be attributed to repeated supratherapeutic doses of acetaminophen remain understudied. METHODS: We conducted a retrospective medical chart review including children aged <5 years admitted with hepatocellular injury. The study was conducted in Bardnesville Junction Hospital operated by Médecins Sans Frontières in Monrovia, Liberia. RESULTS: We analyzed 95 children with liver injury in whom a blood lactate measurement on admission was available. Eighty children (84%) were aged <2 years; 49 children (52%) died during hospitalization. The median acetaminophen concentration on admission was 20 mg/L with 60 (70%) children presenting concentrations exceeding 10 mg/L. Median lactate was significantly higher in children who died (10.7 mmol/L; interquartile range (IQR): 8.5-15.7) than those who survived (6.1 mmol/L; IQR: 4.1-8.5), P value < 0.001). The optimal threshold obtained was 7.2 mmol/L with a sensitivity of 84% and specificity 70% (area under curve = 0.80). The previously established thresholds of 3.5 and 4 mmol/L lactate had very low specificity identifying non-survival in children included in this study. CONCLUSION: In this setting, young children with ALF possibly attributed to acetaminophen toxicity were unlikely to survive if the venous blood lactate concentration exceeded 7.2 mmol/L.

Suspected paracetamol overdose in Monrovia, Liberia: a matched case-control study.

BACKGROUND: A cluster of cases of unexplained multi-organ failure was reported in children at Bardnesville Junction Hospital (BJH), Monrovia, Liberia. Prior to admission, children's caregivers reported antibiotic, antimalarial, paracetamol, and traditional treatment consumption. Since we could not exclude a toxic aetiology, and paracetamol overdose in particular, we implemented prospective syndromic surveillance to better define the clinical characteristics of these children. To investigate risk factors, we performed a case-control study. METHODS: The investigation was conducted in BJH between July 2015 and January 2016. In-hospital syndromic surveillance identified children with at least two of the following symptoms: respiratory distress with normal pulse oximetry while breathing ambient air; altered consciousness; hypoglycaemia; jaundice; and hepatomegaly. After refining the case definition to better reflect potential risk factors for hepatic dysfunction, we selected cases identified from syndromic surveillance for a matched case-control study. Cases were matched with in-hospital and community-based controls by age, sex, month of illness/admission, severity (in-hospital), and proximity of residence (community). RESULTS: Between July and December 2015, 77 case-patients were captured by syndromic surveillance; 68 (88%) were under three years old and 35 (46%) died during hospitalisation. Of these 77, 30 children met our case definition and were matched with 53 hospital and 48 community controls. Paracetamol was the most frequently reported medication taken by the cases and both control groups. The odds of caregivers reporting supra-therapeutic paracetamol consumption prior to admission was higher in cases compared to controls (OR 6.6, 95% CI 2.1-21.3). Plasma paracetamol concentration on day of admission was available for 19 cases and exceeded 10 µg/mL in 10/13 samples collected on day one of admission, and 4/9 (44%) collected on day two. CONCLUSIONS: In a context with limited diagnostic capacity, this study highlights the possibility of supratherapeutic doses of paracetamol as a factor in multi-organ failure in a cohort of children admitted to BJH. In this setting, a careful history of pre-admission paracetamol consumption may alert clinicians to the possibility of overdose, even when confirmatory laboratory analysis is unavailable. Further studies may help define additional toxicological characteristics in such contexts to improve diagnoses.

Correction to: Suspected paracetamol overdose in Monrovia, Liberia: a matched case-control Study.

An amendment to this paper has been published and can be accessed via the original article.

Micro-Hotspots of Risk in Urban Cholera Epidemics.

Targeted interventions have been delivered to neighbors of cholera cases in major epidemic responses globally despite limited evidence for the impact of such targeting. Using data from urban epidemics in Chad and Democratic Republic of the Congo, we estimate the extent of spatiotemporal zones of increased cholera risk around cases. In both cities, we found zones of increased risk of at least 200 meters during the 5 days immediately after case presentation to a clinic. Risk was highest for those living closest to cases and diminished in time and space similarly across settings. These results provide a rational basis for rapidly delivering targeting interventions.

The potential impact of case-area targeted interventions in response to cholera outbreaks: A modeling study.

BACKGROUND: Cholera prevention and control interventions targeted to neighbors of cholera cases (case-area targeted interventions [CATIs]), including improved water, sanitation, and hygiene, oral cholera vaccine (OCV), and prophylactic antibiotics, may be able to efficiently avert cholera cases and deaths while saving scarce resources during epidemics. Efforts to quickly target interventions to neighbors of cases have been made in recent outbreaks, but little empirical evidence related to the effectiveness, efficiency, or ideal design of this approach exists. Here, we aim to provide practical guidance on how CATIs might be used by exploring key determinants of intervention impact, including the mix of interventions, "ring" size, and timing, in simulated cholera epidemics fit to data from an urban cholera epidemic in Africa. METHODS AND FINDINGS: We developed a micro-simulation model and calibrated it to both the epidemic curve and the small-scale spatiotemporal clustering pattern of case households from a large 2011 cholera outbreak in N'Djamena, Chad (4,352 reported cases over 232 days), and explored the potential impact of CATIs in simulated epidemics. CATIs were implemented with realistic logistical delays after cases presented for care using different combinations of prophylactic antibiotics, OCV, and/or point-of-use water treatment (POUWT) starting at different points during the epidemics and targeting rings of various radii around incident case households. Our findings suggest that CATIs shorten the duration of epidemics and are more resource-efficient than mass campaigns. OCV was predicted to be the most effective single intervention, followed by POUWT and antibiotics. CATIs with OCV started early in an epidemic focusing on a 100-m radius around case households were estimated to shorten epidemics by 68% (IQR 62% to 72%), with an 81% (IQR 69% to 87%) reduction in cases compared to uncontrolled epidemics. These same targeted interventions with OCV led to a 44-fold (IQR 27 to 78) reduction in the number of people needed to target to avert a single case of cholera, compared to mass campaigns in high-cholera-risk neighborhoods. The optimal radius to target around incident case households differed by intervention type, with antibiotics having an optimal radius of 30 m to 45 m compared to 70 m to 100 m for OCV and POUWT. Adding POUWT or antibiotics to OCV provided only marginal impact and efficiency improvements. Starting CATIs early in an epidemic with OCV and POUWT targeting those within 100 m of an incident case household reduced epidemic durations by 70% (IQR 65% to 75%) and the number of cases by 82% (IQR 71% to 88%) compared to uncontrolled epidemics. CATIs used late in epidemics, even after the peak, were estimated to avert relatively few cases but substantially reduced the number of epidemic days (e.g., by 28% [IQR 15% to 45%] for OCV in a 100-m radius). While this study is based on a rigorous, data-driven approach, the relatively high uncertainty about the ways in which POUWT and antibiotic interventions reduce cholera risk, as well as the heterogeneity in outbreak dynamics from place to place, limits the precision and generalizability of our quantitative estimates. CONCLUSIONS: In this study, we found that CATIs using OCV, antibiotics, and water treatment interventions at an appropriate radius around cases could be an effective and efficient way to fight cholera epidemics. They can provide a complementary and efficient approach to mass intervention campaigns and may prove particularly useful during the initial phase of an outbreak, when there are few cases and few available resources, or in order to shorten the often protracted tails of cholera epidemics.

Four years of case-based surveillance of meningitis following the introduction of MenAfriVac in Moissala, Chad: lessons learned.

OBJECTIVE: Case-based surveillance of bacterial meningitis in sentinel districts has been recommended after the introduction of the conjugated vaccine against Neisseria meningitidis serogroup A (NmA), MenAfriVac, in the African meningitis belt. Here we report data and lessons learnt from four years of surveillance in the district of Moissala, Chad. METHODS: All suspected cases of meningitis were referred free of charge to the district hospital for lumbar puncture and treatment. Cerebrospinal fluid samples were tested with Pastorex latex agglutination in Moissala, and inoculated trans-isolate media were used for culture and PCR at the national reference laboratory and/or at the Norwegian Institute of Public Health. RESULTS: From July 2012 to December 2016, 237 suspected cases of meningitis were notified, and a specimen was collected from 224. Eighty-three samples were positive for a bacterial pathogen by culture, PCR or Pastorex, including 58 cases due to Streptococcus pneumoniae with only 28 of 49 pneumococcal meningitis confirmed by culture or PCR correctly identified by Pastorex. Four cases of NmA were detected by Pastorex, but none were confirmed by PCR. CONCLUSION: Implementation of case-based surveillance for meningitis is feasible in Chad, but has required political and technical engagement. Given the high proportion of S. pneumoniae and its poor detection by Pastorex, continued use of PCR is warranted for surveillance outside of outbreaks, and efforts to accelerate the introduction of pneumococcal conjugate vaccines are needed. Introduction of MenAfriVac in routine immunisation and future availability of a pentavalent meningococcal conjugate vaccine will be key elements for the sustained reduction in meningitis outbreaks in the area.

Mortality Rates during Cholera Epidemic, Haiti, 2010-2011.

The 2010 cholera epidemic in Haiti was one of the largest cholera epidemics ever recorded. To estimate the magnitude of the death toll during the first wave of the epidemic, we retrospectively conducted surveys at 4 sites in the northern part of Haiti. Overall, 70,903 participants were included; at all sites, the crude mortality rates (19.1-35.4 deaths/1,000 person-years) were higher than the expected baseline mortality rate for Haiti (9 deaths/1,000 person-years). This finding represents an excess of 3,406 deaths (2.9-fold increase) for the 4.4% of the Haiti population covered by these surveys, suggesting a substantially higher cholera mortality rate than previously reported.

Comparison of weight-for-height and mid-upper arm circumference (MUAC) in a therapeutic feeding programme in South Sudan: is MUAC alone a sufficient criterion for admission of children at high risk of mortality?

OBJECTIVE: The present study was performed to describe the operational implications of using mid-upper arm circumference (MUAC) as a single admission criterion for treatment of severe acute malnutrition in South Sudan. DESIGN: We performed a retrospective analysis of routine programme data of children with severe acute malnutrition aged 6-59 months admitted to a therapeutic feeding programme using weight-for-height Z-score (WHZ) and/or MUAC. To understand the implications of using MUAC as a single admission criterion, we compared patient characteristics and treatment outcomes for children admitted with MUAC<115 mm (irrespective of WHZ) v. children admitted with WHZ<-3 and MUAC≥115 mm. RESULTS: Of 2205 children included for analysis, 719 (32·6 %) were admitted to the programme with MUAC<115 mm and 1486 (67·4 %) with WHZ<-3 and MUAC≥115 mm. Children who would have been admitted using a single MUAC<115 mm criterion were more severely malnourished and more likely to be female and younger. Compared with children admitted with WHZ<-3 and MUAC≥115 mm, children who would have been admitted using MUAC<115 mm were less likely to recover (54 % v. 69 %) and had higher risk of death (4 % v. 1 %), but responded to treatment with greater weight and MUAC gains. MUAC<115 mm would have failed to identify 33 % of deaths, while 98 % were identified by WHZ<-3 alone and 100 % by MUAC<130 mm. CONCLUSIONS: The study shows that MUAC<115 mm identified more severely malnourished children with a higher risk of mortality but failed to identify a third of the children who died. Admission criteria for therapeutic feeding should be adapted to the programmatic context with consideration for both operational and public health implications.

Local discrepancies in measles vaccination opportunities: results of population-based surveys in Sub-Saharan Africa.

BACKGROUND: The World Health Organization recommends African children receive two doses of measles containing vaccine (MCV) through routine programs or supplemental immunization activities (SIA). Moreover, children have an additional opportunity to receive MCV through outbreak response immunization (ORI) mass campaigns in certain contexts. Here, we present the results of MCV coverage by dose estimated through surveys conducted after outbreak response in diverse settings in Sub-Saharan Africa. METHODS: We included 24 household-based surveys conducted in six countries after a non-selective mass vaccination campaign. In the majority (22/24), the survey sample was selected using probability proportional to size cluster-based sampling. Others used Lot Quality Assurance Sampling. RESULTS: In total, data were collected on 60,895 children from 2005 to 2011. Routine coverage varied between countries (>95% in Malawi and Kirundo province (Burundi) while <35% in N'Djamena (Chad) in 2005), within a country and over time. SIA coverage was <75% in most settings. ORI coverage ranged from >95% in Malawi to 71.4% [95% CI: 68.9-73.8] in N'Djamena (Chad) in 2005.In five sites, >5% of children remained unvaccinated after several opportunities. Conversely, in Malawi and DRC, over half of the children eligible for the last SIA received a third dose of MCV. CONCLUSIONS: Control pre-elimination targets were still not reached, contributing to the occurrence of repeated measles outbreak in the Sub-Saharan African countries reported here. Although children receiving a dose of MCV through outbreak response benefit from the intervention, ensuring that programs effectively target hard to reach children remains the cornerstone of measles control.