Mass treatment with ivermectin controls onchocerciasis as a public health problem, but it was not known if it could also interrupt transmission and eliminate the parasite in endemic foci in Africa ...where vectors are highly efficient. A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection and transmission, and test whether treatment could be safely stopped. This article reports the results of the final evaluations up to 5 years after the last treatment.
Skin snip surveys were undertaken in 131 villages where 29,753 people were examined and 492,600 blackflies were analyzed for the presence of Onchocerca volvulus larva using a specific DNA probe. There was a declining trend in infection and transmission levels after the last treatment. In two sites the prevalence of microfilaria and vector infectivity rate were zero 3 to 4 years after the last treatment. In the third site, where infection levels were comparatively high before stopping treatment, there was also a consistent decline in infection and transmission to very low levels 3 to 5 years after stopping treatment. All infection and transmission indicators were below postulated thresholds for elimination.
The study has established the proof of principle that onchocerciasis elimination with ivermectin treatment is feasible in at least some endemic foci in Africa. The study results have been instrumental for the current evolution from onchocerciasis control to elimination in Africa.
Mass treatment with ivermectin is a proven strategy for controlling onchocerciasis as a public health problem, but it is not known if it can also interrupt transmission and eliminate the parasite in ...endemic foci in Africa where vectors are highly efficient. A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection and transmission and test whether ivermectin treatment could be safely stopped in the study areas.
Skin snip surveys were undertaken in 126 villages, and 17,801 people were examined. The prevalence of microfilaridermia was <1% in all three foci. A total of 157,500 blackflies were collected and analyzed for the presence of Onchocerca volvulus larvae using a specific DNA probe, and vector infectivity rates were all below 0.5 infective flies per 1,000 flies. Except for a subsection of one focus, all infection and transmission indicators were below postulated thresholds for elimination. Treatment was therefore stopped in test areas of 5 to 8 villages in each focus. Evaluations 16 to 22 months after the last treatment in the test areas involved examination of 2,283 people using the skin snip method and a DEC patch test, and analysis of 123,000 black flies. No infected persons and no infected blackflies were detected in the test areas, and vector infectivity rates in other catching points were <0.2 infective flies per 1,000.
This study has provided the first empirical evidence that elimination of onchocerciasis with ivermectin treatment is feasible in some endemic foci in Africa. Although further studies are needed to determine to what extent these findings can be extrapolated to other endemic areas in Africa, the principle of elimination has been established. The African Programme for Onchocerciasis Control has adopted an additional objective to assess progress towards elimination endpoints in all onchocerciasis control projects and to guide countries on cessation of treatment where feasible.
In Africa, onchocerciasis and lymphatic filariasis (LF) are co-endemic in many areas. Current efforts to eliminate both diseases are through ivermectin-based mass drug administration (MDA). Years of ...ivermectin distribution for onchocerciasis may have interrupted LF transmission in certain areas. The Kédougou region, Senegal, is co-endemic for LF and onchocerciasis. Though MDA for onchocerciasis started in 1988, in 2014 albendazole had not yet been added for LF. The objective of this study was to assess in an integrated manner the LF and onchocerciasis status in the three districts of the Kédougou region after ≥10 years of ivermectin-based MDA. The study employed an African Programme for Onchocerciasis Control (APOC) onchocerciasis-related methodology. In the three districts, 14 villages close to three rivers that have Simulium damnosum breeding sites were surveyed. Convenience sampling of residents ≥5 years old was performed. Assessment for LF antigenemia by immunochromatographic testing (ICT) was added to skin snip microscopy for onchocerciasis. Participants were also tested for antibodies against Wb123 (LF) and Ov16 (onchocerciasis) antigens. In two districts, no participants were ICT or skin snip positive. In the third district, 3.5% were ICT positive and 0.7% were skin snip positive. In all the three districts, Wb123 prevalence was 0.6%. Overall, Ov16 prevalence was 6.9%. Ov16 prevalence among children 5-9 years old in the study was 2.5%. LF antigenemia prevalence was still above treatment threshold in one district despite ≥10 years of ivermectin-based MDA. The presence of Ov16 positive children suggested recent transmission of Onchocerca volvulus. This study showed the feasibility of integrated evaluation of onchocerciasis and LF but development of integrated robust methods for assessing transmission of both LF and onchocerciasis are needed to determine where MDA can be stopped safely in co-endemic areas.
Background Mass treatment with ivermectin controls onchocerciasis as a public health problem, but it was not known if it could also interrupt transmission and eliminate the parasite in endemic foci ...in Africa where vectors are highly efficient. A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection and transmission, and test whether treatment could be safely stopped. This article reports the results of the final evaluations up to 5 years after the last treatment. Methodology/Principal Findings Skin snip surveys were undertaken in 131 villages where 29,753 people were examined and 492,600 blackflies were analyzed for the presence of Onchocerca volvulus larva using a specific DNA probe. There was a declining trend in infection and transmission levels after the last treatment. In two sites the prevalence of microfilaria and vector infectivity rate were zero 3 to 4 years after the last treatment. In the third site, where infection levels were comparatively high before stopping treatment, there was also a consistent decline in infection and transmission to very low levels 3 to 5 years after stopping treatment. All infection and transmission indicators were below postulated thresholds for elimination. Conclusion/Significance The study has established the proof of principle that onchocerciasis elimination with ivermectin treatment is feasible in at least some endemic foci in Africa. The study results have been instrumental for the current evolution from onchocerciasis control to elimination in Africa.
Each year, rotavirus gastroenteritis is responsible for about 37% of deaths from diarrhea among children younger than 5 years of age worldwide, with a disproportionate effect in sub-Saharan Africa.
...We conducted a randomized, placebo-controlled trial in Niger to evaluate the efficacy of a live, oral bovine rotavirus pentavalent vaccine (BRV-PV, Serum Institute of India) to prevent severe rotavirus gastroenteritis. Healthy infants received three doses of the vaccine or placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and were graded on the basis of the score on the Vesikari scale (which ranges from 0 to 20, with higher scores indicating more severe disease). The primary end point was the efficacy of three doses of vaccine as compared with placebo against a first episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score, ≥11) beginning 28 days after dose 3.
Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval CI, 49.9 to 77.9). Similar efficacy was seen in the intention-to-treat analyses, which showed a vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7). There was no significant between-group difference in the risk of adverse events, which were reported in 68.7% of the infants in the vaccine group and in 67.2% of those in the placebo group, or in the risk of serious adverse events (in 8.3% in the vaccine group and in 9.1% in the placebo group); there were 27 deaths in the vaccine group and 22 in the placebo group. None of the infants had confirmed intussusception.
Three doses of BRV-PV, an oral rotavirus vaccine, had an efficacy of 66.7% against severe rotavirus gastroenteritis among infants in Niger. (Funded by Médecins sans Frontières Operational Center and the Kavli Foundation; ClinicalTrials.gov number, NCT02145000 .).
•RotaSIIL has been shown effective against severe rotavirus gastroenteritis in Niger.•Two-year follow-up of the intention-to-treat population shows no safety concerns.•Overall mortality was very low ...for the region.•One case of intussusception was notified, and was unrelated to RotaSIIL.
Rotavirus remains a major cause of diarrhea among children under 5 years of age. The efficacy of RotaSIIL, a pentavalent rotavirus vaccine, was shown in an event-driven trial in Niger. We describe the two-year safety follow-up of this trial.
Follow-up of safety outcomes began upon administration of the first dose of RotaSIIL or placebo. Adverse events were followed until 28 days after the third dose, and serious adverse events were followed until 2 years of age. Suspected cases of intussusception were evaluated at first point of contact and then referred to hospital for surgical evaluation. Causes of death were obtained by chart review and verbal autopsy. Passive surveillance was carried out in health centers. Community health workers carried out active surveillance in villages. Between-group differences were evaluated using the chi-squared test and Fisher’s exact test.
A total of 4092 children were randomized, and 4086 received at least one dose of RotaSIIL or placebo, constituting the intention-to-treat population, who accrued a total of 7385 child-years of follow-up time. At two years of follow-up, 58 (2.8%) participants who received RotaSIIL and 49 (2.4%) participants who received placebo had died (p = 0.38). Most deaths were due to infectious causes common to the study area. One participant had confirmed intussusception, 542 days after receiving the third dose of RotaSIIL. A total of 395 (19.3%) participants receiving RotaSIIL and 419 (20.5%) participants receiving placebo experienced any serious adverse event (p = 0.36). Most serious adverse events were hospitalizations due to infection (malaria, lower respiratory tract infection and gastroenteritis) or marasmus. Overall, 1474 (72.1%) participants receiving RotaSIIL and 1456 (71.1%) participants receiving placebo had at least one adverse event (p = 0.49) in the follow-up period.
At two years of follow-up, RotaSIIL was found to be safe.
Trial registration: ClinicalTrials.gov: NCT02145000.
Due to the rapid development of microbial resistance, finding new molecules became urgent to counteract this problem.
The objective of this work is to access 1,2,3-triazene-1,3-disubstituted, a class ...of molecule with high therapeutic potential.
Here we describe the access to 17 new triazene including six with an imidazole-1,2,3-triazene moiety and eleven with an alkyl-1,2,3-triazene moiety and their evaluation against five strains: two gram (-): Escherichia coli ATCC 25921 and Pseudomonas aeruginosa ATCC 27253; two gram (+) : Staphylococcus aureus ATCC 38213 and Enterococcus faecalis ATCC 29212; and one fungi: Candida albicans ATCC 24433.
All strains were sensitive and the best MIC, 0.28 µM, is observed for 4c against Escherichia coli ATCC 25921. Compound 9, 3-isopropynyltriazene, appears to be the most interesting since it is active on the five evaluated strains with satisfactory MIC 0.32 µM against Escherichia coli and Pseudomonas aeruginosa and 0.64 µM against Enterococcus faecalis and Pseudomonas aeruginosa.
Comparing the structure activity relationship, electron withdrawing groups appear to increase antimicrobial activity.
Abstract Background Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. Pathogen genomic surveillance could be invaluable for monitoring current and emerging ...parasite drug resistance. Methods Data from two decades (2000–2020) of continuous molecular surveillance of P. falciparum parasites from Senegal were retrospectively examined to assess historical changes in malaria drug resistance mutations. Several known drug resistance markers and their surrounding haplotypes were profiled using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole genome sequence based population genomics. Results This dataset was used to track temporal changes in drug resistance markers whose timing correspond to historically significant events such as the withdrawal of chloroquine (CQ) and the introduction of sulfadoxine-pyrimethamine (SP) in 2003. Changes in the mutation frequency at Pfcrt K76T and Pfdhps A437G coinciding with the 2014 introduction of seasonal malaria chemoprevention (SMC) in Senegal were observed. In 2014, the frequency of Pfcrt K76T increased while the frequency of Pfdhps A437G declined. Haplotype-based analyses of Pfcrt K76T showed that this rapid increase was due to a recent selective sweep that started after 2014. Discussion (Conclusion) The rapid increase in Pfcrt K76T is troubling and could be a sign of emerging amodiaquine (AQ) resistance in Senegal. Emerging AQ resistance may threaten the future clinical efficacy of artesunate-amodiaquine (ASAQ) and AQ-dependent SMC chemoprevention. These results highlight the potential of molecular surveillance for detecting rapid changes in parasite populations and stress the need to monitor the effectiveness of AQ as a partner drug for artemisinin-based combination therapy (ACT) and for chemoprevention.
Nutritional status in pregnancy is a key determinant of birth outcomes. In low-income countries, maternal diets are often limited, and daily nutrient supplements are recommended to fill nutrient ...gaps. As a result, it is important to understand the factors influencing acceptability and utilization of nutrient supplements in these settings. Qualitative data (individual interviews and focus group discussions with pregnant women, household members, and study staff) and quantitative data (unannounced household spot checks) were collected in 24 villages in the Maradi region of south-central Niger. Each village was randomly assigned to one of three study arms, with pregnant women receiving either iron and folic acid (IFA) supplements, multiple micronutrient (MMN) supplements, or medium-quantity lipid-based nutrient supplements (MQ-LNS) for daily consumption during pregnancy. Data were collected longitudinally to capture changes in perspective as women progressed through their pregnancy. Participants accepted all three supplement types, and perceived a wide range of health benefits attributed to supplement consumption. However, several important barriers to appropriate consumption were reported, and rumors about the supplements leading to childbirth complications also decreased utilization. The household spot checks suggested that IFA had the highest level of correct consumption. Overall, despite a stated high level of acceptance and enthusiasm for the supplements among participants and their household members, certain fears, side effects, and organoleptic factors led to decreased utilization. The effectiveness of future programs to improve maternal nutritional status through supplementation may be improved by understanding perceived barriers and facilitating factors among participants and tailoring communication efforts appropriately.
Undernutrition is associated with maternal morbidity and poor pregnancy outcomes. This qualitative study seeks to understand the multilevel factors influencing maternal dietary practices in Niger, ...including the impact of pregnancy illnesses on diet. Criterion‐based, purposive sampling was used to select pregnant women and household members from 24 villages in a rural district of the Maradi Region in south‐central Niger. Semistructured interviews (n = 153) and focus group discussions (n = 38) explored 4 primary themes: (a) perceptions of ideal diet during pregnancy, (b) barriers to consuming the ideal diet, (c) coping strategies including dietary responses related to pregnancy illnesses, and (d) changes in perceptions from early to late pregnancy. Longitudinal data collection allowed for repeated interviews of pregnant women to document changes in dietary practices throughout pregnancy. Transcripts were coded using an inductive approach informed by grounded theory methodology. Participants categorized foods into 4 primary dietary taxonomies when discussing ideal maternal diets but cited constraints related to accessibility and availability impeding routine consumption of these foods. Perceptions of “modern,” urban foods as healthy, coupled with key structural barriers such as food costs, were identified. Maternal morbidity influenced food consumption, as women reported reducing food intake early in pregnancy in response to illness episodes. Although awareness of optimal foods for supporting healthy pregnancies was moderately high, some misconceptions were observed and multilevel barriers to food security restricted opportunities for consuming these foods. Nutrition‐specific and nutrition‐sensitive interventions could improve access and availability of acceptable foods for supporting increased dietary intake during pregnancy.
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