Impact of Sulfadoxine-Pyrimethamine Resistance on Effectiveness of Intermittent Preventive Therapy for Malaria in Pregnancy at Clearing Infections and Preventing Low Birth Weight.

BACKGROUND: Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of intermittent preventive therapy in pregnancy (IPTp) with SP is crucial. METHODS: Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus-uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted. RESULTS: Among 1222 parasitemic pregnant women, overall polymerase chain reaction-uncorrected and -corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI], .69-.88; P < .001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI, .67-.97; P = .02). CONCLUSIONS: The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy.

Parasite clearance following treatment with sulphadoxine-pyrimethamine for intermittent preventive treatment in Burkina-Faso and Mali: 42-day in vivo follow-up study.

BACKGROUND: Intermittent Preventive Treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) is widely used for the control of malaria in pregnancy in Africa. The emergence of resistance to SP is a concern requiring monitoring the effectiveness of SP for IPTp. METHODS: This was an in-vivo efficacy study to determine the parasitological treatment response and the duration of post-treatment prophylaxis among asymptomatic pregnant women receiving SP as part of IPTp in Mali and Burkina-Faso. The primary outcome was the PCR-unadjusted % of patients with parasites recurrence by day 42 defined as a positive diagnostic test by malaria smear at any visit between days 4 and 42. Treatment failure was based on the standard World Health Organization criteria. The therapeutic response was estimated using the Kaplan-Meier curve. RESULTS: A total of 580 women were enrolled in Mali (N=268) and Burkina-Faso (N=312) and followed weekly for 42 days. Among these, 94.3% completed the follow-up. The PCR-unadjusted cumulative risk of recurrence by day 42 was 4.9% overall, and 3.2% and 6.5% in Mali and Burkina Faso respectively (Hazard Ratio [HR] =2.14, 95%, CI [0.93-4.90]; P=0.070), and higher among the primi- and secundigravida (6.4%) than multigravida (2.2%, HR=3.01 [1.04-8.69]; P=0.042). The PCR-adjusted failure risk was 1.1% overall (Mali 0.8%, Burkina-Faso 1.4%). The frequencies (95% CI) of the dhfr double and triple mutant and dhps 437 and 540 alleles mutant genotype at enrolment were 24.2% (23.7-25.0), 4.7% (4.4-5.0), and 21.4% (20.8-22.0) and 0.37% (0.29-0.44) in Mali, and 7.1% (6.5-7.7), 44.9% (43.8-46.0) and 75.3% (74.5-76.2) and 0% in Burkina-Faso, respectively. There were no dhfr 164L or dhps 581G mutations. CONCLUSION: SP remains effective at clearing existing infections when provided as IPTp to asymptomatic pregnant women in Mali and Burkina. Continued monitoring of IPTp-SP effectiveness, including of the impact on birth parameters in this region is essential.

Genotype diversity of group A rotavirus strains in children with acute diarrhea in urban Burkina Faso, 2008-2010.

In this study, the diversity of G and P genotypes of rotavirus strains in Burkinabe children were examined. Between November 2008 and February 2010, 447 stool samples were collected from children <5 years of age with acute diarrhea visiting hospital in Ouagadougou. Group A rotavirus was previously detected in 151/447 (33.8%) of the samples tested by an immunochromatographic test and these samples were now tested further for rotavirus G and P genotypes by RT-PCR. Of these, the rotavirus type genes were amplified by RT-PCR for 140/151 (92.7%) samples and G and P genotypes were successfully determined for 81 (57.9%) and 130 (92.9%) samples, respectively. The most prevalent G genotypes were G1, 34/140 (24.3%), and G9, 21/140 (15%), while the predominant P genotypes were P[6], 56/140 (40%), and P[8], 54/140 (38.6%). Among the single infections, 63/140 (45%), the predominant G/P combinations were: G1P[8] (33%), G9P[8] (29%), and G2P[6] (14%). The unusual strains G1P[9] (3%), G12P[6] (3%), G10P[6] (2%), and G2P[8] (2%) were also detected. In a high number of strains 61/140 (43.6%), the G genotype could not be determined and mixed infections were determined in 17/140 (12.1%) of strains identified. This study highlights the high diversity and presence of unusual rotavirus strains in children in Burkina Faso.

Epidemiology of rotavirus infection among young children with acute diarrhoea in Burkina Faso.

BACKGROUND: In anticipation of vaccine introduction, we assessed epidemiology of rotavirus disease among children visiting medical centre due to acute diarrhoea in Ouagadougou, Burkina Faso. METHODS: Between November 2008 and February 2010, stool specimens from 447 children less than 5 years of age suffering from diarrhoea were tested for the presence of rotavirus by antigen detection using an immunochromatographic test. Sociodemographic, environmental and clinical factors were assessed during the study. RESULTS: Rotavirus antigen was detected in 151 (33.8%) of the patients. Most of the cases (94.2%) were in children < 24 months of age. Fever and vomiting were the symptoms most commonly reported in association with rotavirus diarrhoea and the patients were often hospitalized. Rotavirus-associated diarrhoea occurred mostly during the season from December to April (dry season). Rotavirus infection was significantly less frequent in breast-fed than among bottle-fed babies. CONCLUSIONS: The results of this study underscore the need to control rotavirus infections among young children in Burkina Faso and may argue a decision on the introduction of rotavirus vaccine in Burkina Faso.

Modelling the incremental benefit of introducing malaria screening strategies to antenatal care in Africa.

Plasmodium falciparum in pregnancy is a major cause of adverse pregnancy outcomes. We combine performance estimates of standard rapid diagnostic tests (RDT) from trials of intermittent screening and treatment in pregnancy (ISTp) with modelling to assess whether screening at antenatal visits improves upon current intermittent preventative therapy with sulphadoxine-pyrimethamine (IPTp-SP). We estimate that RDTs in primigravidae at first antenatal visit are substantially more sensitive than in non-pregnant adults (OR = 17.2, 95% Cr.I. 13.8-21.6), and that sensitivity declines in subsequent visits and with gravidity, likely driven by declining susceptibility to placental infection. Monthly ISTp with standard RDTs, even with highly effective drugs, is not superior to monthly IPTp-SP. However, a hybrid strategy, recently adopted in Tanzania, combining testing and treatment at first visit with IPTp-SP may offer benefit, especially in areas with high-grade SP resistance. Screening and treatment in the first trimester, when IPTp-SP is contraindicated, could substantially improve pregnancy outcomes.

External Quality Assessment of Bacterial Identification and Antimicrobial Susceptibility Testing in African National Public Health Laboratories, 2011-2016.

Background: In 2002, the World Health Organization (WHO) launched a regional microbiology external quality assessment (EQA) programme for national public health laboratories in the African region, initially targeting priority epidemic-prone bacterial diseases, and later including other common bacterial pathogens. Objectives: The aim of this study was to analyse the efficacy of an EQA programme as a laboratory quality system evaluation tool. Methods: We analysed the proficiency of laboratories' performance of bacterial identification and antimicrobial susceptibility testing (AST) for the period 2011-2016. The National Institute for Communicable Diseases of South Africa provided technical coordination following an agreement with WHO, and supplied EQA samples of selected bacterial organisms for microscopy (Gram stain), identification, and antimicrobial susceptibility testing (AST). National public health laboratories, as well as laboratories involved in the Invasive Bacterial Diseases Surveillance Network, were enrolled by the WHO Regional Office for Africa to participate in the EQA programme. We analysed participants' results of 41 surveys, which included the following organisms sent as challenges: Streptococcus pneumonia, Haemophilus influenzae, Neisseria meningitidis, Salmonella Typhi, Salmonella Enteritidis, Shigella flexneri, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus anginosus, Enterococcus faecium, Serratia marcescens, Acinetobacter baumannii, and Enterobacter cloacae. Results: Eighty-one laboratories from 45 countries participated. Overall, 76% of participants obtained acceptable scores for identification, but a substantial proportion of AST scores were not in the acceptable range. Of 663 assessed AST responses, only 42% had acceptable scores. Conclusion: In the African Region, implementation of diagnostic stewardship in clinical bacteriology is generally suboptimal. This report illustrates that AST is poorly done compared to microscopy and identification. It is critically important to make the case for implementation of quality assurance in AST, as it is the cornerstone of antimicrobial resistance surveillance reporting and implementation of the Global Antimicrobial Resistance Surveillance System.

Community-based promotional campaign to improve uptake of intermittent preventive antimalarial treatment in pregnancy in Burkina Faso.

Malaria preventive strategies in pregnancy were assessed in a health center randomized trial comparing intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) with and without community based promotional activities in rural Burkina Faso. The study involved 2,240 secundigravidae and secundigravidae and evaluated factors associated with antenatal clinic (ANC) attendance and uptake of IPTp-SP. With promotion, 64.2% completed > or = 3 ANC visits compared with 44.7% without (P = 0.05). Complete uptake of IPTp-SP was 71.8% with and 49.1% without promotion (P = 0.008). The IPTp-SP uptake was lowest in adolescents delivering during high malaria transmission with (29%) or without promotion (30%). Uptake of SP was higher during the low transmission season than in the high transmission season (adjusted odds ratio = 2.17, 95% confidence interval = 1.59-3.03). Community sensitization increased ANC attendance and IPTp-SP uptake. Adolescents were the most difficult to reach, particularly during the high malaria transmission period. The impact of IPTp-SP will be limited unless this high risk group is protected.