Effectiveness of typhoid conjugate vaccine in Zimbabwe used in response to an outbreak among children and young adults: A matched case control study.

BACKGROUND: Zimbabwe suffers from regular outbreaks of typhoid fever (TF), worse since 2017. Most cases were in Harare and a vaccination campaign with Typhoid Conjugate Vaccine (TCV) was conducted in March 2019. The vaccine effectiveness (VE) was assessed against culture-confirmed S. Typhi in children six months to 15 years and in individuals six months to 45 years in Harare. METHODS: A matched case-control study was conducted in three urban suburbs of Harare targeted by the TCV vaccination campaign. Suspected TF cases were enrolled prospectively in four health facilities and were matched to facility (1:1) and community (1:5) controls. FINDINGS: Of 504 suspected cases from July 2019 to March 2020, 148 laboratory-confirmed TF cases and 153 controls confirmed-negative were identified. One hundred and five (47 aged six months to 15 years) cases were age, sex, and residence matched with 105 facility-based controls while 96 cases were matched 1:5 by age, sex, and immediate-neighbour with 229 community controls. The adjusted VE against confirmed TF was 75% (95%CI: 1-94, p = 0.049) compared to facility controls, and 84% (95%CI: 57-94, p < 0.001) compared to community controls in individuals six months to 15 years. The adjusted VE against confirmed TF was 46% (95%CI: 26-77, p = 0.153) compared to facility controls, and 67% (95%CI: 35-83, p = 0.002) compared to community controls six months to 45 years old. INTERPRETATION: This study confirms that one vaccine dose of TCV is effective to control TF in children between six months and 15 years old in an African setting.

A feasibility study using mid-upper arm circumference as the sole anthropometric criterion for admission and discharge in the outpatient treatment for severe acute malnutrition.

BACKGROUND: The World Health Organization recommends the use of a weight-for-height Z-score (WHZ) and/or mid-upper arm circumference (MUAC) as anthropometric criteria for the admission and discharge of young children for the community-based management of severe acute malnutrition. However, using MUAC as a single anthropometric criterion for admission and discharge in therapeutic nutritional programs may offer operational advantages to simplify admission processes at therapeutic nutritional centers and improve program coverage. METHODS: This pragmatic, non-randomized, intervention study compared a standard outpatient nutritional program (n = 824) for the treatment of uncomplicated severe acute malnutrition using WHZ < - 3 and/or MUAC< 115 mm and/or bipedal edema for admission and discharge to a program (n = 1019) using MUAC as the sole anthropometric criterion for admission (MUAC< 120 mm) and discharge (MUAC ≥125 mm at two consecutive visits) in the Tahoua Region of Niger. RESULTS: Compared to the standard program, the MUAC-only program discharged more children as recovered (70.1% vs. 51.6%; aOR 2.31, 95%CI 1.79-2.98) and fewer children as non-respondent or defaulters, based on respective program definitions. The risk of non-response was high in both programs. Three months post-discharge, children who were discharged after recovery in the MUAC-only program had lower WHZ and MUAC measures. Sixty-three children ineligible for the MUAC-only program but eligible for a standard program (MUAC ≥120 mm and WHZ < -3) were followed for twelve weeks and the anthropometric status of 69.8% of these children did not deteriorate (i.e. MUAC ≥120 mm) despite not immediately receiving treatment in the MUAC-only program. CONCLUSIONS: The results from this study share the first operational experience of using MUAC as sole anthropometric criterion for admission and discharge in Niger and overall support the consideration for MUAC-only programming: the MUAC-only model of care was associated with a higher recovery and a lower defaulter rate than the standard program with very few children found to be excluded from treatment with an admission criterion of MUAC < 120 mm. Further consideration of the appropriate MUAC-based discharge criterion as it relates to an increased risk of non-response and adverse post-discharge outcomes would be prudent.

High cholera vaccination coverage following emergency campaign in Haiti: Results from a cluster survey in three rural Communes in the South Department, 2017.

Oral cholera vaccine (OCV) has increasingly been used as an outbreak control measure, but vaccine shortages limit its application. A two-dose OCV campaign targeting residents aged over 1 year was launched in three rural Communes of Southern Haiti during an outbreak following Hurricane Matthew in October 2016. Door-to-door and fixed-site strategies were employed and mobile teams delivered vaccines to hard-to-reach communities. This was the first campaign to use the recently pre-qualified OCV, Euvichol. The study objective was to estimate post-campaign vaccination coverage in order to evaluate the campaign and guide future outbreak control strategies. We conducted a cluster survey with sampling based on random GPS points. We identified clusters of five households and included all members eligible for vaccination. Local residents collected data through face-to-face interviews. Coverage was estimated, accounting for the clustered sampling, and 95% confidence intervals calculated. 435 clusters, 2,100 households and 9,086 people were included (99% response rate). Across the three communes respectively, coverage by recall was: 80.7% (95% CI:76.8-84.1), 82.6% (78.1-86.4), and 82.3% (79.0-85.2) for two doses and 94.2% (90.8-96.4), 91.8% (87-94.9), and 93.8% (90.8-95.9) for at least one dose. Coverage varied by less than 9% across age groups and was similar among males and females. Participants obtained vaccines from door-to-door vaccinators (53%) and fixed sites (47%). Most participants heard about the campaign through community 'criers' (58%). Despite hard-to-reach communities, high coverage was achieved in all areas through combining different vaccine delivery strategies and extensive community mobilisation. Emergency OCV campaigns are a viable option for outbreak control and where possible multiple strategies should be used in combination. Euvichol will help alleviate the OCV shortage but effectiveness studies in outbreaks should be done.

Feasibility of engaging caregivers in at-home surveillance of children with uncomplicated severe acute malnutrition.

Many factors can contribute to low coverage of treatment for severe acute malnutrition (SAM), and a limited number of health facilities and trained personnel can constrain the number of children that receive treatment. Alternative models of care that shift the responsibility for routine clinical and anthropometric surveillance from the health facility to the household could reduce the burden of care associated with frequent facility-based visits for both healthcare providers and caregivers. To assess the feasibility of shifting clinical surveillance to caregivers in the outpatient management of SAM, we conducted a pilot study to assess caregivers' understanding and retention of key concepts related to the surveillance of clinical danger signs and anthropometric measurement over a 28-day period. At the time of a child's admission to nutritional treatment, a study nurse provided a short training to groups of caregivers on two topics: (a) clinical danger signs in children with SAM that warrant facility-based care and (b) methods to measure and monitor their child's mid-upper arm circumference. Caregiver understanding was assessed using standardized questionnaires before training, immediately after training, and 28 days after training. Knowledge of most clinical danger signs (e.g., convulsions, edema, poor appetite, respiratory distress, and lethargy) was low (0-45%) before training but increased immediately after and was retained 28 days after training. Agreement between nurse-caregiver mid-upper arm circumference colour classifications was 77% (98/128) immediately after training and 80% after 28 days. These findings lend preliminary support to pursue further study of alternative models of care that allow for greater engagement of caregivers in the clinical and anthropometric surveillance of children with SAM.

Hand hygiene compliance and environmental contamination with gram-negative bacilli in a rural hospital in Madarounfa, Niger.

BACKGROUND: Healthcare-associated infections pose a major, yet often preventable risk to patient safety. Poor hand hygiene among healthcare personnel and unsanitary hospital environments may contribute to this risk in low-income settings. We aimed to describe hand hygiene behaviour and environmental contamination by season in a rural, sub-Saharan African hospital setting. METHODS: We conducted a concurrent triangulation mixed-methods study combining three types of data at a hospital in Madarounfa, Niger. Hand hygiene observations among healthcare personnel during two seasons contributed quantitative data describing hand hygiene frequency and its variability in relation to seasonal changes in caseload. Semistructured interviews with healthcare personnel contributed qualitative data on knowledge, attitudes and barriers to hand hygiene. Biweekly environmental samples evaluated microbial contamination from October 2016 to December 2017. Triangulation identified convergences, complements and contradictions across results. RESULTS: Hand hygiene compliance, or the proportion of actions (handrubbing or handwashing) performed out of all actions required, was low (11% during non-peak and 36% during peak caseload seasons). Interviews with healthcare personnel suggesting good general knowledge of hand hygiene contradicted the low hand hygiene compliance. However, compliance by healthcare activity was convergent with poor knowledge of precise hand hygiene steps and the motivation to prevent personal acquisition of infection identified during interviews. Contamination of environmental samples with gram-negative bacilli was high (45%), with the highest rates of contamination observed during the peak caseload season. CONCLUSION: Low hand hygiene compliance coupled with high contamination rates of hospital environments may increase the risk of hospital-acquired infections in sub-Saharan African settings.

A screening tool for psychological difficulties in children aged 6 to 36 months: cross-cultural validation in Kenya, Cambodia and Uganda.

BACKGROUND: In low-resource settings, the lack of mental health professionals and cross-culturally validated screening instruments complicates mental health care delivery. This is especially the case for very young children. Here, we aimed to develop and cross-culturally validate a simple and rapid tool, the PSYCa 6-36, that can be administered by non-professionals to screen for psychological difficulties among children aged six to 36 months. METHODS: A primary validation of the PSYCa 6-36 was conducted in Kenya (n = 319 children aged 6 to 36 months; 2014), followed by additional validations in Kenya (n = 215; 2014) Cambodia (n = 189; 2015) and Uganda (n = 182; 2016). After informed consent, trained interviewers administered the PSYCa 6-36 to caregivers participating in the study. We assessed the psychometric properties of the PSYCa 6-36 and external validity was assessed by comparing the results of the PSYCa 6-36 against a clinical global impression severity [CGIS] score rated by an independent psychologist after a structured clinical interview with each participant. RESULTS: The PSYCa 6-36 showed satisfactory psychometric properties (Cronbach's alpha > 0.60 in Uganda and > 0.70 in Kenya and Cambodia), temporal stability (intra-class correlation coefficient [ICC] > 0.8), and inter-rater reliability (ICC from 0.6 in Uganda to 0.8 in Kenya). Psychologists identified psychological difficulties (CGIS score > 1) in 11 children (5.1%) in Kenya, 13 children (8.7%) in Cambodia and 15 (10.5%) in Uganda, with an area under the receiver operating characteristic curve of 0.65 in Uganda and 0.80 in Kenya and Cambodia. CONCLUSIONS: The PSYCa 6-36 allowed for rapid screening of psychological difficulties among children aged 6 to 36 months among the populations studied. Use of the tool also increased awareness of children's psychological difficulties and the importance of early recognition to prevent long-term consequences. The PSYCa 6-36 would benefit from further use and validation studies in popula`tions with higher prevalence of psychological difficulties.

Antimicrobial treatment practices among Ugandan children with suspicion of central nervous system infection.

Acute central nervous system (CNS) infections in children in sub-Saharan Africa are often fatal. Potential contributors include late presentation, limited diagnostic capacity and inadequate treatment. A more nuanced understanding of treatment practices with a goal of optimizing such practices is critical to prevent avoidable case fatality. We describe empiric antimicrobial treatment, antibiotic resistance and treatment adequacy in a prospective cohort of 459 children aged two months to 12 years hospitalised for suspected acute CNS infections in Mbarara, Uganda, from 2009 to 2012. Among these 459 children, 155 had a laboratory-confirmed diagnosis of malaria (case-fatality rate [CFR] 14%), 58 had bacterial infections (CFR 24%) and 6 children had mixed malaria and bacterial infections (CFR 17%). Overall case fatality was 18.1% (n = 83). Of 219 children with laboratory-confirmed malaria and/or bacterial infections, 182 (83.1%) received an adequate antimalarial and/or antibiotic on the day of admission and 211 (96.3%) within 48 hours of admission. The proportion of those receiving adequate treatment was similar among survivors and non-survivors. All bacterial isolates were sensitive to ceftriaxone except one Escherichia coli isolate with extended-spectrum beta-lactamase (ESBL). The observed high mortality was not a result of inadequate initial antimicrobial treatment at the hospital. The epidemiology of CNS infection in this setting justifies empirical use of a third-generation cephalosporin, however antibiotic resistance should be monitored closely.

Carriage prevalence and serotype distribution of Streptococcus pneumoniae prior to 10-valent pneumococcal vaccine introduction: A population-based cross-sectional study in South Western Uganda, 2014.

BACKGROUND: Information on Streptococcus pneumoniae nasopharyngeal (NP) carriage before the pneumococcal conjugate vaccine (PCV) introduction is essential to monitor impact. The 10-valent PCV (PCV10) was officially introduced throughout Ugandan national childhood immunization programs in 2013 and rolled-out countrywide during 2014. We aimed to measure the age-specific Streptococcus pneumoniae carriage and serotype distribution across all population age groups in the pre-PCV10 era in South Western Uganda. METHODS: We conducted a two-stage cluster, age-stratified, cross-sectional community-based study in Sheema North sub-district between January and March 2014. One NP swab was collected and analyzed for each participant in accordance with World Health Organization guidelines. RESULTS: NP carriage of any pneumococcal serotype was higher among children <2years old (77%; n=387) than among participants aged ≥15years (8.5%; n=325) (chi2 p<0.001). Of the 623 positive cultures, we identified 49 serotypes among 610 (97.9%) isolates; thirteen (2.1%) isolates were non-typeable. Among <2years old, serotypes 6A, 6B, 14, 15B, 19F and 23F accounted for half of all carriers. Carriage prevalence with PCV10 serotypes was 29.4% among individuals aged <2years (n=387), 23.4% in children aged 2-4years (n=217), 11.4% in 5-14years (n=417), and 0.4% among individuals ≥15years of age (n=325). The proportion of carried pneumococci serotypes contained in PCV10 was 38.1% (n=291), 32.8% (n=154), 29.4% (n=156), and 4.4% (n=22) among carriers aged <2years, 2-4years, 5-14years and ≥15years, respectively. DISCUSSION: In Sheema district, the proportion of PCV10 serotypes was low (<40%), across all age groups, especially among individuals aged 15years or older (<5%). PCV10 introduction is likely to impact transmission among children and to older individuals, but less likely to substantially modify pneumococcal NP ecology among individuals aged 15years or older.

Aetiology and Outcomes of Suspected Infections of the Central Nervous System in Children in Mbarara, Uganda.

Infections of the central nervous system (CNS) are severe conditions, leading to neurological sequelae or death. Knowledge of the causative agents is essential to develop guidelines for case management in resource-limited settings. Between August 2009 and October 2012, we conducted a prospective descriptive study of the aetiology of suspected CNS infections in children two months to 12 years old, with fever and at least one sign of CNS involvement in Mbarara Hospital, Uganda. Children were clinically evaluated on admission and discharge, and followed-up for 6 months for neurological sequelae. Pathogens were identified from cerebrospinal fluid (CSF) and blood using microbiological and molecular methods. We enrolled 459 children. Plasmodium falciparum (36.2%) and bacteria in CSF (13.3%) or blood (3.3%) were the most detected pathogens. Viruses were found in 27 (5.9%) children. No pathogen was isolated in 207 (45.1%) children. Patterns varied by age and HIV status. Eighty-three (18.1%) children died during hospitalisation, and 23 (5.0%) during follow-up. Forty-one (13.5%) children had neurological sequelae at the last visit. While malaria remains the main aetiology in children with suspected CNS infections, no pathogen was isolated in many children. The high mortality and high rate of neurological sequelae highlight the need for efficient diagnosis.

Outpatient treatment of severe acute malnutrition: response to treatment with a reduced schedule of therapeutic food distribution.

Background: Community-based management of severe acute malnutrition (SAM) has been shown to be safe and cost-effective, but program coverage remains low. Treatment models that maintain high levels of clinical effectiveness but allow for increased coverage are still needed. A reduced schedule of follow-up, in which children receive clinical follow-up and therapeutic foods on a monthly rather than weekly basis, may be one alternative.Objective: We aimed to describe the safety and feasibility of a monthly distribution of ready-to-use therapeutic food (RUTF) in the treatment of uncomplicated SAM, in terms of clinical response to treatment and household RUTF use.Design: We conducted a nonrandomized pilot intervention study in which 115 children eligible for outpatient treatment of SAM were provided a monthly ration of RUTF. Anthropometric measurements were taken weekly for 4 wk to monitor treatment response. Unannounced household spot checks were conducted over 4 wk to assess household use of RUTF and storage practices.Results: Adequate weight and midupper arm circumference (MUAC) gain were found throughout the 4-wk follow-up period. Observed mean ± SD weight gain from admission was 9.8 ± 6.8 g · kg-1 · d-1 in week 1 and 4.2 ± 2.1 g · kg-1 · d-1 by week 4. Unplanned household spot checks found an average surplus of RUTF sachets compared with the number expected based on the date of distribution and recommended dosing throughout the 4 wk of follow-up. The frequency at which more than the recommended dose was used (i.e., deviance of >2 sachets between available and expected stocks) was 4% and 22% of households visited in week 1 and week 4, respectively.Conclusion: Adequate treatment response and RUTF use in the outpatient treatment of SAM was maintained over 4 wk of follow-up with a monthly schedule of RUTF distribution. This study was registered at clinicaltrials.gov as NCT02994212.

Detection Yield and Tolerability of String Test for Diagnosis of Childhood Intrathoracic Tuberculosis.

BACKGROUND: Difficulty to obtain sputum in children complicates diagnosis of intrathoracic tuberculosis (TB). The intragastric string test (ST) used for retrieval of enteric pathogens might be an alternative specimen collection method but requires further evaluation of its utility in TB diagnosis. We conducted a cross-sectional study comparing the TB detection yield and the tolerability of ST and sputum induction (SI) in children. METHODS: Two ST and SI procedures were performed in children (3-14 years of age) who were clinically suspected of having TB. The string was removed after a 2-hour gastric downtime, and SI was done after a maximum of 20 minutes nebulization with 5% saline solution. LED-fluorescence microscopy and mycobacterial cultures were performed on all specimens, and XpertMTB/RIF assay was performed on stored specimen sediments. Tolerability questionnaires were administered to parents of children. RESULTS: Of 137 included children (median age: 8.1 years; 33.3% with HIV infection), 14 (10.2%) were diagnosed with TB, 10 (71.4%) by ST and 12 (85.7%) by SI. Among 105 children with both ST and SI performed, 5 (4.8%) versus 4 (3.8%) were smear positive using ST and SI, respectively (McNemar P = 1.00). Nine (8.6%) in each group had positive cultures (P = 1.00). Of 64 children tested with XpertMTB/RIF, 3 (4.7%) of the ST group versus 4 (6.3%) of the SI group were TB positive (P = 1.00). No adverse serious events were reported. ST could not be performed in 22 of 137 (16.1%) children because they were unable to swallow the capsule. CONCLUSIONS: TB detection yield was comparable between ST and SI. The tolerability of ST in young children might be improved by the reduction of the size of the capsule.

Determinants of Visceral Leishmaniasis: A Case-Control Study in Gedaref State, Sudan.

BACKGROUND: Improving knowledge on local determinants of visceral leishmaniasis (VL) is crucial to guide the development of relevant control strategies. This study aimed to identify individual and household level determinants of primary VL in 24 highly endemic villages of Tabarak Allah hospital's catchment area, Gedaref State, Sudan. METHODS: From September 2012 to July 2013, in an unmatched case-control design, 198 patients with primary VL were compared to 801 controls free of VL symptoms and with a negative VL rapid test. Using random spatial sampling, controls were selected with a distribution of age, sex and village of residence proportionate to the distribution of the target population. Data were collected using a structured questionnaire. RESULTS: Children and men were at higher risk of VL. Reporting VL patient(s) in the household in the previous year was the strongest VL risk factor. In a multivariate analysis, VL risk increased with household size, sleep location (outside the yard, not in the farm), evening outdoor activities in the rainy season (playing, watching TV, radio listening), use of ground nut oil as animal repellent and of smoke of Acacia seyal as indoor repellent, presence of dogs in the yard at night, Acacia nilotica in the yard's immediate surroundings and of a forest at eye range. VL risk appeared to decrease with the use of drinking water sources other than the village water tank, a buffer distance from the adjacent house yard, and with the presence of animals other than dogs in the yard at night. In contrast with previous studies, housing factors, mosquito-net use, black cotton soil, ethnicity, socioeconomic index, presence of Balanites aegyptica and Azadirachta indica in the yard were not independent VL determinants. DISCUSSION AND CONCLUSION: Although these results do not provide evidence of causality, they provide useful suggestions for guiding further intervention studies on VL preventive measures.

Malaria PCR detection in Cambodian low-transmission settings: dried blood spots versus venous blood samples.

In the context of malaria elimination, novel strategies for detecting very low malaria parasite densities in asymptomatic individuals are needed. One of the major limitations of the malaria parasite detection methods is the volume of blood samples being analyzed. The objective of the study was to compare the diagnostic accuracy of a malaria polymerase chain reaction assay, from dried blood spots (DBS, 5 µL) and different volumes of venous blood (50 µL, 200 µL, and 1 mL). The limit of detection of the polymerase chain reaction assay, using calibrated Plasmodium falciparum blood dilutions, showed that venous blood samples (50 µL, 200 µL, 1 mL) combined with Qiagen extraction methods gave a similar threshold of 100 parasites/mL, ∼100-fold lower than 5 µL DBS/Instagene method. On a set of 521 field samples, collected in two different transmission areas in northern Cambodia, no significant difference in the proportion of parasite carriers, regardless of the methods used was found. The 5 µL DBS method missed 27% of the samples detected by the 1 mL venous blood method, but most of the missed parasites carriers were infected by Plasmodium vivax (84%). The remaining missed P. falciparum parasite carriers (N = 3) were only detected in high-transmission areas.

Descriptive epidemiology of typhoid fever during an epidemic in Harare, Zimbabwe, 2012.

BACKGROUND: Typhoid fever remains a significant public health problem in developing countries. In October 2011, a typhoid fever epidemic was declared in Harare, Zimbabwe - the fourth enteric infection epidemic since 2008. To orient control activities, we described the epidemiology and spatiotemporal clustering of the epidemic in Dzivaresekwa and Kuwadzana, the two most affected suburbs of Harare. METHODS: A typhoid fever case-patient register was analysed to describe the epidemic. To explore clustering, we constructed a dataset comprising GPS coordinates of case-patient residences and randomly sampled residential locations (spatial controls). The scale and significance of clustering was explored with Ripley K functions. Cluster locations were determined by a random labelling technique and confirmed using Kulldorff's spatial scan statistic. PRINCIPAL FINDINGS: We analysed data from 2570 confirmed and suspected case-patients, and found significant spatiotemporal clustering of typhoid fever in two non-overlapping areas, which appeared to be linked to environmental sources. Peak relative risk was more than six times greater than in areas lying outside the cluster ranges. Clusters were identified in similar geographical ranges by both random labelling and Kulldorff's spatial scan statistic. The spatial scale at which typhoid fever clustered was highly localised, with significant clustering at distances up to 4.5 km and peak levels at approximately 3.5 km. The epicentre of infection transmission shifted from one cluster to the other during the course of the epidemic. CONCLUSIONS: This study demonstrated highly localised clustering of typhoid fever during an epidemic in an urban African setting, and highlights the importance of spatiotemporal analysis for making timely decisions about targetting prevention and control activities and reinforcing treatment during epidemics. This approach should be integrated into existing surveillance systems to facilitate early detection of epidemics and identify their spatial range.

Plasmodium prevalence and artemisinin-resistant falciparum malaria in Preah Vihear Province, Cambodia: a cross-sectional population-based study.

BACKGROUND: Intensified efforts are urgently needed to contain and eliminate artemisinin-resistant Plasmodium falciparum in the Greater Mekong subregion. Médecins Sans Frontières plans to support the Ministry of Health in eliminating P. falciparum in an area with artemisinin resistance in the north-east of Cambodia. As a first step, the prevalence of Plasmodium spp. and the presence of mutations associated with artemisinin resistance were evaluated in two districts of Preah Vihear Province. METHODS: A cross-sectional population-based study using a two-stage cluster sampling was conducted in the rural districts of Chhaeb and Chey Saen, from September to October 2013. In each district, 30 clusters of 10 households were randomly selected. In total, blood samples were collected for 1,275 participants in Chhaeb and 1,224 in Chey Saen. Prevalence of Plasmodium spp. was assessed by PCR on dried blood spots. Plasmodium falciparum positive samples were screened for mutations in the K13-propeller domain gene (PF3D7_1343700). RESULT: The prevalence of Plasmodium spp. was estimated at 1.49% (95% CI 0.71-3.11%) in Chhaeb and 2.61% (95% CI 1.45-4.66%) in Chey Saen. Twenty-seven samples were positive for P. falciparum, giving a prevalence of 0.16% (95% CI 0.04-0.65) in Chhaeb and 2.04% (95% CI 1.04-3.99%) in Chey Saen. Only 4.0% of the participants testing positive presented with fever or history of fever. K13-propeller domain mutant type alleles (C580Y and Y493H) were found, only in Chey Saen district, in seven out of 11 P. falciparum positive samples with enough genetic material to allow testing. CONCLUSION: The overall prevalence of P. falciparum was low in both districts but parasites presenting mutations in the K13-propeller domain gene, strongly associated with artemisinin-resistance, are circulating in Chey Saen.The prevalence might be underestimated because of the absentees - mainly forest workers - and the workers of private companies who were not included in the study. These results confirm the need to urgently develop and implement targeted interventions to contain and eliminate P. falciparum malaria in this district before it spreads to other areas.

Time is (still) of the essence: quantifying the impact of emergency meningitis vaccination response in Katsina State, Nigeria.

BACKGROUND: In 2009, a large meningitis A epidemic affected a broad region of northern Nigeria and southern Niger, resulting in more than 75 000 cases and 4000 deaths. In collaboration with state and federal agencies, Médecins Sans Frontières (MSF) intervened with a large-scale vaccination campaign using polysaccharide vaccine. Here the authors analyze the impact (cases averted) of the vaccination response as a function of the timing and coverage achieved. METHODS: Phenomenological epidemic models were fitted to replicate meningitis surveillance data from the Nigerian Ministry of Health/WHO surveillance system and from reinforced surveillance conducted by MSF in both vaccinated and unvaccinated areas using a dynamic, state-space framework to account for under-reporting of cases. RESULTS: The overall impact of the vaccination campaigns (reduction in meningitis cases) in Katsina State, northern Nigeria, ranged from 4% to 12%. At the local level, vaccination reduced cases by as much as 50% when campaigns were conducted early in the epidemic. CONCLUSIONS: Reactive vaccination with polysaccharide vaccine during meningitis outbreaks can significantly reduce the case burden when conducted early and comprehensively. Introduction of the conjugate MenAfriVac vaccine has reduced rates of disease caused by serogroup A Neisseria meningitidis in the region. Despite this, reactive campaigns with polysaccharide vaccine remain a necessary and important tool for meningitis outbreak response.

Burden of visceral leishmaniasis in villages of eastern Gedaref State, Sudan: an exhaustive cross-sectional survey.

BACKGROUND: Since December 2009, Médecins Sans Frontières has diagnosed and treated patients with visceral leishmaniasis (VL) in Tabarak Allah Hospital, eastern Gedaref State, one of the main endemic foci of VL in Sudan. A survey was conducted to estimate the VL incidence in villages around Tabarak Allah. METHODS: Between the 5(th) of May and the 17(th) of June 2011, we conducted an exhaustive door-to-door survey in 45 villages of Al-Gureisha locality. Deaths were investigated by verbal autopsies. All individuals with (i) fever of at least two weeks, (ii) VL diagnosed and treated in the previous year, and (iii) clinical suspicion of post-kala-azar dermal leishmaniasis (PKDL) were referred to medical teams for case ascertainment. A new case of VL was a clinical suspect with a positive rk39 rapid test or direct agglutination test (DAT). RESULTS: In the 45 villages screened, 17,702 households were interviewed, for a population of 94,369 inhabitants. The crude mortality rate over the mean recall period of 409 days was 0.13/10'000 people per day. VL was a possible or probable cause for 19% of all deaths. The VL-specific mortality rate was estimated at 0.9/1000 per year. The medical teams examined 551 individuals referred for a history of fever of at least two weeks. Out of these, 16 were diagnosed with primary VL. The overall incidence of VL over the past year was 7.0/1000 persons per year, or 7.9/1000 per year when deaths possibly or probably due to VL were included. Overall, 12.5% (11,943/95,609) of the population reported a past VL treatment episode. DISCUSSION AND CONCLUSION: VL represents a significant health burden in eastern Gedaref State. Active VL case detection had a very low yield in this specific setting with adequate access to care and may not be the priority intervention to enhance control in similar contexts.

Performance of small cluster surveys and the clustered LQAS design to estimate local-level vaccination coverage in Mali.

BACKGROUND: Estimation of vaccination coverage at the local level is essential to identify communities that may require additional support. Cluster surveys can be used in resource-poor settings, when population figures are inaccurate. To be feasible, cluster samples need to be small, without losing robustness of results. The clustered LQAS (CLQAS) approach has been proposed as an alternative, as smaller sample sizes are required. METHODS: We explored (i) the efficiency of cluster surveys of decreasing sample size through bootstrapping analysis and (ii) the performance of CLQAS under three alternative sampling plans to classify local VC, using data from a survey carried out in Mali after mass vaccination against meningococcal meningitis group A. RESULTS: VC estimates provided by a 10 × 15 cluster survey design were reasonably robust. We used them to classify health areas in three categories and guide mop-up activities: i) health areas not requiring supplemental activities; ii) health areas requiring additional vaccination; iii) health areas requiring further evaluation. As sample size decreased (from 10 × 15 to 10 × 3), standard error of VC and ICC estimates were increasingly unstable. Results of CLQAS simulations were not accurate for most health areas, with an overall risk of misclassification greater than 0.25 in one health area out of three. It was greater than 0.50 in one health area out of two under two of the three sampling plans. CONCLUSIONS: Small sample cluster surveys (10 × 15) are acceptably robust for classification of VC at local level. We do not recommend the CLQAS method as currently formulated for evaluating vaccination programmes.

Adherence to self-administered tuberculosis treatment in a high HIV-prevalence setting: a cross-sectional survey in Homa Bay, Kenya.

BACKGROUND: Good adherence to treatment is crucial to control tuberculosis (TB). Efficiency and feasibility of directly observed therapy (DOT) under routine program conditions have been questioned. As an alternative, Médecins sans Frontières introduced self-administered therapy (SAT) in several TB programs. We aimed to measure adherence to TB treatment among patients receiving TB chemotherapy with fixed dose combination (FDC) under SAT at the Homa Bay district hospital (Kenya). A second objective was to compare the adherence agreement between different assessment tools. METHODS: We conducted a cross-sectional survey amongst a series of new TB patients receiving 6 months of standard TB chemotherapy with FDC under SAT. Adherence was assessed at home with urine testing for Isoniazid (INH), pill count, interviewer-administered questionnaire and visual analogue scale (VAS). RESULTS: In November 2008 and in June 2009, 212 of 279 eligible patients were assessed for adherence. Overall, 95.2% [95%CI: 91.3-97.7] of the patients reported not having missed a tablet in the last 4 days. On the VAS, complete adherence was estimated at 92.5% [95%CI: 88.0-95.6]. INH urine test was positive for 97.6% [95%CI: 94.6-99.2] of the patients. Pill count could be assessed among only 70% of the interviewed patients. Among them, it was complete for 82.3% [95%CI: 75.1-88.1]. Among the 212 surveyed patients, 193 (91.0%) were successfully treated (cured or treatment completed). The data suggest a fair agreement between the questionnaire and the INH urine test (k = 0.43) and between the questionnaire and the VAS (k = 0.40). Agreement was poor between the other adherence tools. CONCLUSION: These results suggest that SAT, together with the FDC, allows achieving appropriate adherence to antituberculosis treatment in a high TB and HIV burden area. The use of a combination of a VAS and a questionnaire can be an adequate approach to monitor adherence to TB treatment in routine program conditions.

Effectiveness of ready-to-use therapeutic food compared to a corn/soy-blend-based pre-mix for the treatment of childhood moderate acute malnutrition in Niger.

Standard nutritional treatment of moderate acute malnutrition (MAM) relies on fortified blended flours though their importance to treat this condition is a matter of discussion. With the newly introduced World Health Organization growth standards, more children at an early stage of malnutrition will be treated following the dietary protocols as for severe acute malnutrition, including ready-to-use therapeutic food (RUTF). We compared the effectiveness of RUTF and a corn/soy-blend (CSB)-based pre-mix for the treatment of MAM in the supplementary feeding programmes (SFPs) supported by Médecins Sans Frontières, located in the Zinder region (south of Niger). Children measuring 65 to <110 cm, newly admitted with MAM [weight-for-height (WHM%) between 70% and <80% of the NCHS median] were randomly allocated to receive either RUTF (Plumpy'Nut®, 1000 kcal day(-1)) or a CSB pre-mix (1231 kcal day(-1)). Other interventions were similar in both groups (e.g. weekly family ration and ration at discharge). Children were followed weekly up to recovery (WHM% ≥ 85% for 2 consecutive weeks). In total, 215 children were recruited in the RUTF group and 236 children in the CSB pre-mix group with an overall recovery rate of 79.1 and 64.4%, respectively (p < 0.001). There was no evidence for a difference between death, defaulter and non-responder rates. More transfers to the inpatient Therapeutic Feeding Centre (I-TFC) were observed in the CSB pre-mix group (19.1%) compared to the RUTF group (9.3%) (p = 0.003). The average weight gain up to discharge was 1.08 g kg(-1) day(-1) higher in the RUTF group [95% confidence interval: 0.46-1.70] and the length of stay was 2 weeks shorter in the RUTF group (p < 0.001). For the treatment of childhood MAM in Niger, RUTF resulted in a higher weight gain, a higher recovery rate, a shorter length of stay and a lower transfer rate to the I-TFC compared to a CSB pre-mix. This might have important implications on the efficacy and the quality of SFPs.