Journal Article > ResearchAbstract Only
Journal of the National Cancer Institute . 18 March 2025; DOI:10.1093/jnci/djaf054
Befano B, Kalpathy-Cramer J, Egemen D, Inturrisi F, Jeronimo J, et al.
Journal of the National Cancer Institute . 18 March 2025; DOI:10.1093/jnci/djaf054
The HPV-Automated Visual Evaluation (PAVE) Consortium is validating a cervical screening strategy enabling accurate cervical screening in resource-limited settings. A rapid, low-cost HPV assay permits sensitive HPV testing of self-collected vaginal specimens; HPV-negative women are reassured. Triage of positives combines HPV genotyping (four groups in order of cancer risk) and visual inspection assisted by automated cervical visual evaluation (AVE) that classifies cervical appearance as severe, indeterminate, or normal. Together, the combination predicts which women have precancer, permitting targeted management to those most needing treatment.
We analyzed CIN3+ yield for each PAVE risk level (HPV genotype crossed by AVE classification) from nine clinical sites (Brazil, Cambodia, Dominican Republic, El Salvador, Eswatini, Honduras, Malawi, Nigeria, and Tanzania). Data from 1832 HPV-positive participants confirmed that HPV genotype and AVE classification each strongly and independently predict risk of histologic CIN3+. The combination of these low-cost tests provided excellent risk stratification, warranting pre-implementation demonstration projects.
Conference Material > Poster
Titulaer P
MSF Paediatric Days 2024. 3 May 2024; DOI:10.57740/ctQIcdD1A
Journal Article > ResearchFull Text
Clin Pharmacol Ther
Clinical Pharmacology and Therapeutics. 1 May 2024; Volume 115 (Issue 5); 1105-1113.; DOI:10.1002/cpt.3174
Chupradit S, Wamalwa DC, Maleche‐Obimbo E, Kekitiinwa AR, Mwanga‐Amumpaire J, et al.
Clin Pharmacol Ther
Clinical Pharmacology and Therapeutics. 1 May 2024; Volume 115 (Issue 5); 1105-1113.; DOI:10.1002/cpt.3174
Antiretroviral therapy for children living with HIV (CLHIV) under 3 years of age commonly includes lopinavir/ritonavir (LPV/r). However, the original liquid LPV/r formulation has taste and cold storage difficulties. To address these challenges, LPV/r oral pellets have been developed. These pellets can be mixed with milk or food for administration and do not require refrigeration. We developed the population pharmacokinetic (PK) model and assessed drug exposure of LPV/r oral pellets administered twice daily to CLHIV per World Health Organization (WHO) weight bands. The PK analysis included Kenyan and Ugandan children participating in the LIVING studies (NCT02346487) receiving LPV/r pellets (40/10 mg) and ABC/3TC (60/30 mg) dispersible tablets. Population PK models were developed for lopinavir (LPV) and ritonavir (RTV) to evaluate the impact of RTV on the oral clearance (CL/F) of LPV. The data obtained from the study were analyzed using nonlinear mixed‐effects modeling approach. Data from 514 children, comprising a total of 2,998 plasma concentrations of LPV/r were included in the analysis. The LPV and RTV concentrations were accurately represented by a one‐compartment model with first‐order absorption (incorporating a lag‐time) and elimination. Body weight influenced LPV and RTV PK parameters. The impact of RTV concentrations on the CL/F of LPV was characterized using a maximum effect model. Simulation‐predicted target LPV exposures were achieved in children with this pellet formulation across the WHO weight bands. The LPV/r pellets dosed in accordance with WHO weight bands provide adequate LPV exposures in Kenyan and Ugandan children weighing 3.0 to 24.9 kg.
Journal Article > ReviewFull Text
E Clinical Medicine. 11 March 2024; Volume 70; 102508.; DOI:10.1016/j.eclinm.2024.102508
Ruef M, Emonet S, Merglen A, Dewez JE, Obama BM, et al.
E Clinical Medicine. 11 March 2024; Volume 70; 102508.; DOI:10.1016/j.eclinm.2024.102508
BACKGROUND
The increasing resistance of Enterobacterales to third-generation cephalosporins and carbapenems in sub-Saharan Africa (SSA) is a major public health concern. We did a systematic review and meta-analysis of studies to estimate the carriage prevalence of Enterobacterales not susceptible to third-generation cephalosporins or carbapenems among paediatric populations in SSA.
METHODS
We performed a systematic literature review and meta-analysis of cross-sectional and cohort studies to estimate the prevalence of childhood (0-18 years old) carriage of extended-spectrum cephalosporin-resistant Enterobacterales (ESCR-E) or carbapenem-resistant Enterobacterales (CRE) in SSA. Medline, EMBASE and the Cochrane Library were searched for studies published from 1 January 2005 to 1 June 2022. Studies with <10 occurrences per bacteria, case reports, and meta-analyses were excluded. Quality and risk of bias were assessed using the Newcastle-Ottawa scale. Meta-analyses of prevalences and odds ratios were calculated using generalised linear mixed-effects models. Heterogeneity was assessed using I2 statistics. The protocol is available on PROSPERO (CRD42021260157).
FINDINGS
Of 1111 studies examined, 40 met our inclusion criteria, reporting on the carriage prevalence of Enterobacterales in 9408 children. The pooled carriage prevalence of ESCR-E was 32.2% (95% CI: 25.2%-40.2%). Between-study heterogeneity was high (I2 = 96%). The main sources of bias pertained to participant selection and the heterogeneity of the microbiological specimens. Carriage proportions were higher among sick children than healthy ones (35.7% vs 16.9%). The pooled proportion of nosocomial acquisition was 53.8% (95% CI: 32.1%-74.1%) among the 922 children without ESCR-E carriage at hospital admission. The pooled odds ratio of ESCR-E carriage after antibiotic treatment within the previous 3 months was 3.20 (95% CI: 2.10-4.88). The proportion of pooled carbapenem-resistant for Enterobacterales was 3.6% (95% CI: 0.7%-16.4%).
INTERPRETATION
This study suggests that ESCR-E carriage among children in SSA is frequent. Microbiology capacity and infection control must be scaled-up to reduce the spread of those multidrug-resistant microorganisms.
The increasing resistance of Enterobacterales to third-generation cephalosporins and carbapenems in sub-Saharan Africa (SSA) is a major public health concern. We did a systematic review and meta-analysis of studies to estimate the carriage prevalence of Enterobacterales not susceptible to third-generation cephalosporins or carbapenems among paediatric populations in SSA.
METHODS
We performed a systematic literature review and meta-analysis of cross-sectional and cohort studies to estimate the prevalence of childhood (0-18 years old) carriage of extended-spectrum cephalosporin-resistant Enterobacterales (ESCR-E) or carbapenem-resistant Enterobacterales (CRE) in SSA. Medline, EMBASE and the Cochrane Library were searched for studies published from 1 January 2005 to 1 June 2022. Studies with <10 occurrences per bacteria, case reports, and meta-analyses were excluded. Quality and risk of bias were assessed using the Newcastle-Ottawa scale. Meta-analyses of prevalences and odds ratios were calculated using generalised linear mixed-effects models. Heterogeneity was assessed using I2 statistics. The protocol is available on PROSPERO (CRD42021260157).
FINDINGS
Of 1111 studies examined, 40 met our inclusion criteria, reporting on the carriage prevalence of Enterobacterales in 9408 children. The pooled carriage prevalence of ESCR-E was 32.2% (95% CI: 25.2%-40.2%). Between-study heterogeneity was high (I2 = 96%). The main sources of bias pertained to participant selection and the heterogeneity of the microbiological specimens. Carriage proportions were higher among sick children than healthy ones (35.7% vs 16.9%). The pooled proportion of nosocomial acquisition was 53.8% (95% CI: 32.1%-74.1%) among the 922 children without ESCR-E carriage at hospital admission. The pooled odds ratio of ESCR-E carriage after antibiotic treatment within the previous 3 months was 3.20 (95% CI: 2.10-4.88). The proportion of pooled carbapenem-resistant for Enterobacterales was 3.6% (95% CI: 0.7%-16.4%).
INTERPRETATION
This study suggests that ESCR-E carriage among children in SSA is frequent. Microbiology capacity and infection control must be scaled-up to reduce the spread of those multidrug-resistant microorganisms.
Journal Article > ReviewFull Text
E Clinical Medicine. 8 March 2024; Volume 70; 102512.; DOI:10.1016/j.eclinm.2024.102512
Kowalski M, Minka Obama B, Catho G, Dewez JE, Merglen A, et al.
E Clinical Medicine. 8 March 2024; Volume 70; 102512.; DOI:10.1016/j.eclinm.2024.102512
BACKGROUND
The burden of antimicrobial resistance (AMR) has been estimated to be the highest in sub-Saharan Africa (SSA). The current study estimated the proportion of drug-resistant Enterobacterales causing infections in SSA children.
METHODS
We searched MEDLINE/PubMed, Embase and the Cochrane Library to identify retrospective and prospective studies published from 01/01/2005 to 01/06/2022 reporting AMR of Enterobacterales causing infections in sub-Saharan children (0-18 years old). Studies were excluded if they had unclear documentation of antimicrobial susceptibility testing methods or fewer than ten observations per bacteria. Data extraction and quality appraisal were conducted by two authors independently. The primary outcome was the proportion of Enterobacterales resistant to antibiotics commonly used in paediatrics. Proportions were combined across studies using mixed-effects logistic regression models per bacteria and per antibiotic. Between-study heterogeneity was assessed using the I2 statistic. The protocol was registered with PROSPERO (CRD42021260157).
FINDINGS
After screening 1111 records, 122 relevant studies were included, providing data on more than 30,000 blood, urine and stool isolates. Escherichia coli and Klebsiella spp. were the predominant species, both presenting high proportions of resistance to third-generation cephalosporins, especially in blood cultures: 40.6% (95% CI: 27.7%-55%; I2: 85.7%, number of isolates (n): 1032) and 84.9% (72.8%-92.2%; I2: 94.1%, n: 2067), respectively. High proportions of resistance to other commonly used antibiotics were also observed. E. coli had high proportions of resistance, especially for ampicillin (92.5%; 95% CI: 76.4%-97.9%; I2: 89.8%, n: 888) and gentamicin (42.7%; 95% CI: 30%-56.5%; I2: 71.9%, n: 968). Gentamicin-resistant Klebsiella spp. were also frequently reported (77.6%; 95% CI: 65.5%-86.3%; I2: 91.6%, n: 1886).
INTERPRETATION
High proportions of resistance to antibiotics commonly used for empirical treatment of infectious syndromes were found for Enterobacterales in sub-Saharan children. There is a critical need to better identify local patterns of AMR to inform and update clinical guidelines for better treatment outcomes.
The burden of antimicrobial resistance (AMR) has been estimated to be the highest in sub-Saharan Africa (SSA). The current study estimated the proportion of drug-resistant Enterobacterales causing infections in SSA children.
METHODS
We searched MEDLINE/PubMed, Embase and the Cochrane Library to identify retrospective and prospective studies published from 01/01/2005 to 01/06/2022 reporting AMR of Enterobacterales causing infections in sub-Saharan children (0-18 years old). Studies were excluded if they had unclear documentation of antimicrobial susceptibility testing methods or fewer than ten observations per bacteria. Data extraction and quality appraisal were conducted by two authors independently. The primary outcome was the proportion of Enterobacterales resistant to antibiotics commonly used in paediatrics. Proportions were combined across studies using mixed-effects logistic regression models per bacteria and per antibiotic. Between-study heterogeneity was assessed using the I2 statistic. The protocol was registered with PROSPERO (CRD42021260157).
FINDINGS
After screening 1111 records, 122 relevant studies were included, providing data on more than 30,000 blood, urine and stool isolates. Escherichia coli and Klebsiella spp. were the predominant species, both presenting high proportions of resistance to third-generation cephalosporins, especially in blood cultures: 40.6% (95% CI: 27.7%-55%; I2: 85.7%, number of isolates (n): 1032) and 84.9% (72.8%-92.2%; I2: 94.1%, n: 2067), respectively. High proportions of resistance to other commonly used antibiotics were also observed. E. coli had high proportions of resistance, especially for ampicillin (92.5%; 95% CI: 76.4%-97.9%; I2: 89.8%, n: 888) and gentamicin (42.7%; 95% CI: 30%-56.5%; I2: 71.9%, n: 968). Gentamicin-resistant Klebsiella spp. were also frequently reported (77.6%; 95% CI: 65.5%-86.3%; I2: 91.6%, n: 1886).
INTERPRETATION
High proportions of resistance to antibiotics commonly used for empirical treatment of infectious syndromes were found for Enterobacterales in sub-Saharan children. There is a critical need to better identify local patterns of AMR to inform and update clinical guidelines for better treatment outcomes.
Journal Article > Case Report/SeriesFull Text
Oxf Med Case Reports. 27 January 2024; Volume 2024 (Issue 1); omad147.; DOI:10.1093/omcr/omad147
Phillipo D, Lucas S, Kalunga MP, Inyasi E, Lebba JP, et al.
Oxf Med Case Reports. 27 January 2024; Volume 2024 (Issue 1); omad147.; DOI:10.1093/omcr/omad147
False-negative qualitative Human Chorionic Gonadotropin (hCG) result is a phenomenon in which large amounts of β-hCG are produced by molar pregnancy, oversaturating the test’s assay system and leading to false-negative results known as the ‘prozone phenomenon’ or the ‘hook effect’. This can lead to misdiagnosis and delay in management despite high suspicious clinical and ultrasound findings. We report a case of an 18-year-old female who presented to our health facility with amenorrhea of 16 weeks, lower abdominal pain, soft and large fundal height for gestational age, and cramping with slight per-vaginal bleeding, and a negative urinary pregnancy test (UPT). Based on clinical presentation, ultrasound findings and a positive UPT after urine dilution, molar pregnancy was diagnosed. Aspiration was performed under ultrasound guidance, and follow-up was done as per MSF guidelines. HCPs need to be familiar with some rare cases for which the possibility of finding false-negative UPT is likely.
Journal Article > ResearchFull Text
Int J Infect Dis. 1 September 2022; Volume 122; 215-221.; DOI:10.1016/j.ijid.2022.05.039
Zheng Q, Luquero FJ, Ciglenecki I, Wamala JF, Abubakar A, et al.
Int J Infect Dis. 1 September 2022; Volume 122; 215-221.; DOI:10.1016/j.ijid.2022.05.039
BACKGROUND
Cholera remains a public health threat but is inequitably distributed across sub-Saharan Africa. Lack of standardized reporting and inconsistent outbreak definitions limit our understanding of cholera outbreak epidemiology.
METHODS
From a database of cholera incidence and mortality, we extracted data from sub-Saharan Africa and reconstructed outbreaks of suspected cholera starting in January 2010 to December 2019 based on location-specific average weekly incidence rate thresholds. We then described the distribution of key outbreak metrics.
RESULTS
We identified 999 suspected cholera outbreaks in 744 regions across 25 sub-Saharan African countries. The outbreak periods accounted for 1.8 billion person-months (2% of the total during this period) from January 2010 to January 2020. Among 692 outbreaks reported from second-level administrative units (e.g., districts), the median attack rate was 0.8 per 1000 people (interquartile range (IQR), 0.3-2.4 per 1000), the median epidemic duration was 13 weeks (IQR, 8-19), and the median early outbreak reproductive number was 1.8 (range, 1.1-3.5). Larger attack rates were associated with longer times to outbreak peak, longer epidemic durations, and lower case fatality risks.
CONCLUSIONS
This study provides a baseline from which the progress toward cholera control and essential statistics to inform outbreak management in sub-Saharan Africa can be monitored.
Cholera remains a public health threat but is inequitably distributed across sub-Saharan Africa. Lack of standardized reporting and inconsistent outbreak definitions limit our understanding of cholera outbreak epidemiology.
METHODS
From a database of cholera incidence and mortality, we extracted data from sub-Saharan Africa and reconstructed outbreaks of suspected cholera starting in January 2010 to December 2019 based on location-specific average weekly incidence rate thresholds. We then described the distribution of key outbreak metrics.
RESULTS
We identified 999 suspected cholera outbreaks in 744 regions across 25 sub-Saharan African countries. The outbreak periods accounted for 1.8 billion person-months (2% of the total during this period) from January 2010 to January 2020. Among 692 outbreaks reported from second-level administrative units (e.g., districts), the median attack rate was 0.8 per 1000 people (interquartile range (IQR), 0.3-2.4 per 1000), the median epidemic duration was 13 weeks (IQR, 8-19), and the median early outbreak reproductive number was 1.8 (range, 1.1-3.5). Larger attack rates were associated with longer times to outbreak peak, longer epidemic durations, and lower case fatality risks.
CONCLUSIONS
This study provides a baseline from which the progress toward cholera control and essential statistics to inform outbreak management in sub-Saharan Africa can be monitored.
Journal Article > ReviewFull Text
Trop Med Int Health. 16 January 2021; Volume 26 (Issue 5); 504-517.; DOI:10.1111/tmi.13550
Nair MM, Mahajan R, Burza S, Zeegers MP
Trop Med Int Health. 16 January 2021; Volume 26 (Issue 5); 504-517.; DOI:10.1111/tmi.13550
OBJECTIVES
To explore the current evidence on interventions to influence antibiotic prescribing behaviour of health professionals in outpatient settings in low‐income and lower‐middle‐income countries, an underrepresented area in the literature.
METHODS
The systematic review protocol for this study was registered in PROSPERO (CRD42020170504). We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies relating to antibiotic prescribing of health professionals in outpatient settings in low‐income and lower‐middle‐income countries. Behavioural interventions were classified as persuasive, enabling, restrictive, structural or bundle (mix of different interventions). In total, 3,514 abstracts were screened and 42 studies were selected for full‐text review, with 13 studies included in the final narrative synthesis.
RESULTS
Of the 13 included studies, five were conducted in Vietnam, two in Sudan, two in Tanzania, two in India and two in Kenya. All studies were conducted in the outpatient or ambulatory setting: eight took place in primary health centres, two in private clinics and three in pharmacies. Our review found that enabling or educational interventions alone may not be sufficient to overcome the ingrained incentives to link revenue generation to sales of antibiotics, and hence, their inappropriate prescription or misuse. Bundle interventions appear to be very effective at changing prescription behaviour among healthcare providers, including drug sellers and pharmacists.
CONCLUSIONS
Multi‐faceted bundle interventions that combine regulation enforcement with face‐to‐face education and peer influence may be more effective than educational interventions alone at curbing inappropriate antibiotic use.
To explore the current evidence on interventions to influence antibiotic prescribing behaviour of health professionals in outpatient settings in low‐income and lower‐middle‐income countries, an underrepresented area in the literature.
METHODS
The systematic review protocol for this study was registered in PROSPERO (CRD42020170504). We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies relating to antibiotic prescribing of health professionals in outpatient settings in low‐income and lower‐middle‐income countries. Behavioural interventions were classified as persuasive, enabling, restrictive, structural or bundle (mix of different interventions). In total, 3,514 abstracts were screened and 42 studies were selected for full‐text review, with 13 studies included in the final narrative synthesis.
RESULTS
Of the 13 included studies, five were conducted in Vietnam, two in Sudan, two in Tanzania, two in India and two in Kenya. All studies were conducted in the outpatient or ambulatory setting: eight took place in primary health centres, two in private clinics and three in pharmacies. Our review found that enabling or educational interventions alone may not be sufficient to overcome the ingrained incentives to link revenue generation to sales of antibiotics, and hence, their inappropriate prescription or misuse. Bundle interventions appear to be very effective at changing prescription behaviour among healthcare providers, including drug sellers and pharmacists.
CONCLUSIONS
Multi‐faceted bundle interventions that combine regulation enforcement with face‐to‐face education and peer influence may be more effective than educational interventions alone at curbing inappropriate antibiotic use.
Journal Article > Case Report/SeriesFull Text
Oxf Med Case Reports. 24 June 2019; Volume 2019 (Issue 6); omz049.; DOI:10.1093/omcr/omz049
Najera Villagrana SM, Garcia Naranjo Santisteban A
Oxf Med Case Reports. 24 June 2019; Volume 2019 (Issue 6); omz049.; DOI:10.1093/omcr/omz049
Tungiasis is a highly prevalent yet neglected disease of populations affected by extreme poverty. It causes great discomfort and pain, leads to social stigmatization and, when left untreated, can cause serious complications. Although natural repellents have been shown to be effective, too little is being done in terms of systematic prevention and treatment. In addition, self-treatment (usually extraction of fleas with non-sterile sharp instruments) comports high risks of infection, notably with viral hepatitis and human immunodeficiency virus. In this article, we report seven severe cases of tungiasis in children living in a refugee camp in Tanzania, all of whom were treated with surgical extraction of the fleas because the topical treatment (dimethicone) was not available. Refugee camps-particularly in sub-Saharan Africa where tungiasis is endemic-should be considered high-risk areas for the condition. Aid organizations should engage in active case searching, and health promotion should be systematically carried out.
Journal Article > ResearchFull Text
Public Health Action. 21 June 2013; Volume 3 (Issue 2); 156-159.; DOI:10.5588/pha.12.0103
Kilale AM, Ngowi BJ, Mfinanga GS, Egwaga S, Doulla B, et al.
Public Health Action. 21 June 2013; Volume 3 (Issue 2); 156-159.; DOI:10.5588/pha.12.0103
SETTING
One reference and three zonal laboratories and 500 health facilities managing retreatment tuberculosis (TB) patients in Tanzania.
OBJECTIVES
The National Tuberculosis and Leprosy Programme (NTLP) requires that all notified cases of retreatment TB in Tanzania have sputum samples sent for culture and drug susceptibility testing (DST). This study determined 1) if the number of annually notified retreatment patients corresponded to the number of sputum samples received by the reference laboratories, and 2) the number of culture-positive samples and the number of cases undergoing DST.
DESIGN
Nine-year audit of country-wide programme data from 2002 to 2010.
RESULTS
Of the 40 940 retreatment TB patients notified by the NTLP, 3871 (10%) had their sputum samples received at the reference and zonal laboratories for culture and DST. A total of 3761 (97%) sputum samples were processed for culture, of which 1589 (42%) were found to be culture-positive and 1415 (89%) had DST performed.
CONCLUSIONS
There is a >90% shortfall between notified retreatment cases and numbers of sputum samples received, cultured and assessed for DST at reference and zonal laboratories. Steps needed to address this problem are discussed.
One reference and three zonal laboratories and 500 health facilities managing retreatment tuberculosis (TB) patients in Tanzania.
OBJECTIVES
The National Tuberculosis and Leprosy Programme (NTLP) requires that all notified cases of retreatment TB in Tanzania have sputum samples sent for culture and drug susceptibility testing (DST). This study determined 1) if the number of annually notified retreatment patients corresponded to the number of sputum samples received by the reference laboratories, and 2) the number of culture-positive samples and the number of cases undergoing DST.
DESIGN
Nine-year audit of country-wide programme data from 2002 to 2010.
RESULTS
Of the 40 940 retreatment TB patients notified by the NTLP, 3871 (10%) had their sputum samples received at the reference and zonal laboratories for culture and DST. A total of 3761 (97%) sputum samples were processed for culture, of which 1589 (42%) were found to be culture-positive and 1415 (89%) had DST performed.
CONCLUSIONS
There is a >90% shortfall between notified retreatment cases and numbers of sputum samples received, cultured and assessed for DST at reference and zonal laboratories. Steps needed to address this problem are discussed.