Detection of Artemisinin Resistance Marker Kelch-13 469Y in Plasmodium falciparum, South Kivu, Democratic Republic of the Congo, 2022.

Partial artemisinin resistance has emerged in East Africa, posing a threat to malaria control across the continent. The Democratic Republic of the Congo carries one of the heaviest malaria burdens globally, and the South Kivu province directly borders current artemisinin resistance hot spots, but indications of such resistance have not been observed so far. We assessed molecular markers of antimalarial drug resistance in 256 Plasmodium falciparum isolates collected in 2022 in South Kivu, Democratic Republic of the Congo. One isolate carried the P. falciparum Kelch-13 469Y variant, a marker associated with partial artemisinin resistance and decreased lumefantrine susceptibility in Uganda. In addition, the multidrug resistance-1 mutation pattern suggested increased lumefantrine tolerance.

Hyperglycemia and elevated C-reactive protein are independent predictors of hospital mortality in hospitalized COVID-19 patients in South-Kivu, eastern Democratic Republic of the Congo: A cross-sectional study.

Background and Aim: The coronavirus disease 2019 (COVID-19) pandemic was a priority public health problem because of its high mortality rate. This study mainly aimed to determine factors associated with a poor outcome in COVID-19 hospitalized patients in South-Kivu, an eastern province of the Democratic Republic of the Congo (DRC). Methods: This observational study retrospectively evaluated medical records of patients consecutively admitted for probable or confirmed COVID-19 between May 01 and July 31, 2020 at the Hôpital Provincial Général de Référence de Bukavu (HPGRB), a tertiary hospital located in South-Kivu. A binary logistic regression model was performed to determine the predictors of mortality. Results: A total of 157 hospitalized COVID-19 patients aged 57.7 (13.2) years were included in this study. Male gender (69.4%), older age (52.9%), medical history of diabetes (38.2%), and arterial hypertension (35.1%) were the most frequent risk factors. Most patients presented with fever (73.3%), cough (72.6%), and dyspnea (66.2%). Overall, 45.1% of patients died. Intrahospital mortality was significantly associated with advanced age [odds ratio, OR (95% confidence interval, CI) = 2.34 (1.06-5.38)], hypoxemia [OR (95% CI) = 4.67 (2.02-10.77)], hyperglycemia [OR (95% CI) = 2.14 (1.06-4.31)], kidney failure [OR (95% CI) = 2.82 (1.4-5.68)], hyperleukocytosis [OR (95% CI) = 3.33 (1.67-6.66)], and higher C-reactive protein (CRP) levels [OR (95% CI) = 3.93 (1.93-8.01)]. After adjustment for various covariates, only higher CRP levels [OR (95% CI) = 3.23 (1.23-8.5)] and hyperglycemia [OR (95% CI) = 2.5 (1.02-6.11)] at admission were independently associated with mortality. Conclusion: Hyperglycemia and marked inflammatory syndrome were the major predictors of poor outcomes in patients hospitalized for COVID-19 in South-Kivu. These two factors should be quantified at hospital admission to establish the patient's prognosis.

Probiotics for children with uncomplicated severe acute malnutrition (PruSAM study): A randomized controlled trial in the Democratic Republic of Congo.

BACKGROUND: Severe acute malnutrition (SAM) contributes to nearly 1 million deaths annually worldwide, with diarrhea and pneumonia being the common morbidity associated with mortality. OBJECTIVES: To assess the effect of probiotics on diarrhea, pneumonia, and nutritional recovery in children with uncomplicated SAM. METHODS: A randomized, double-blind, placebo-controlled study was conducted involving 400 children with uncomplicated SAM randomly assigned to ready-to-use therapeutic food (RUTF) either with (n = 200) or without (n = 200) probiotics. Patients received 1 mL daily dose of a blend of Lacticasebacillus rhamnosus GG and Limosilactobacillus reuteri DSM 17938 (dosage, 2 billion colony-forming units; 50:50) or placebo during 1 mo. They were simultaneously fed with the RUTF for 6 to 12 wk, depending on patients' recovery rates. The primary outcome was the duration of diarrhea. Secondary outcomes included diarrheal and pneumonic incidence, nutritional recovery, and transfer to inpatient care rate. RESULTS: For children with diarrhea, the number of days of disease was lower in the probiotic group (4.11; 95% CI: 3.37, 4.51) than that in the placebo group (6.68; 95% CI: 6.26, 7.13; P < 0.001). For children aged 16 mo or older, the risk of diarrhea was lower in the probiotic group (75.6%; 95% CI: 66.2, 82.9) than that in the placebo group (95.0%; 95% CI: 88.2, 97.9; P < 0.001), but no significant difference of the risk for the youngest. In the probiotic group, nutritional recovery happened earlier: at the 6th wk, 40.6% of the infants were waiting for nutritional recovery, contrasting with 68.7% of infants in the placebo group; but the nutritional recovery rate at the 12th wk was similar between the groups. Probiotics had no effect on pneumonic incidence and transfer to inpatient care. CONCLUSIONS: This trial supports using probiotics for the treatment of children with uncomplicated SAM. Its effect on diarrhea could positively affect nutritional programs in resource-limited settings. This trial was registered https://pactr.samrc.ac.za as PACTR202108842939734.

Revisiting Konzo Risk Factors in Three Areas Differently Affected by Spastic Paraparesis in Eastern Democratic Republic of the Congo Discloses a Prominent Role of the Nutritional Status-A Comparative Cross-Sectional Study.

This comparative cross-sectional study aimed to better understand the respective contributions of protein malnutrition and cassava-derived cyanide poisoning in the development of konzo. We compared data on nutritional status and cyanide exposure of school-age adolescent konzo-diseased patients to those of non-konzo subjects of similar age from three areas in the Eastern Democratic Republic of the Congo. Our results show that konzo patients had a high prevalence of both wasting (54.5%) and stunting (72.7%), as well as of cyanide poisoning (81.8%). Controls from Burhinyi and those from Idjwi showed a similar profile with a low prevalence of wasting (3.3% and 6.5%, respectively) and intermediate prevalence of stunting (26.7% and 23.9%, respectively). They both had a high prevalence of cyanide poisoning (50.0% and 63.0%, respectively), similar to konzo-patients. On the other hand, controls from Bukavu showed the lowest prevalence of both risk factors, namely chronic malnutrition (12.1%) and cyanide poisoning (27.6%). In conclusion, cassava-derived cyanide poisoning does not necessarily coexist with konzo outbreaks. The only factor differentiating konzo patients from healthy individuals exposed to cyanide poisoning appeared to be their worse nutritional status. This further suggests that, besides the known role of cyanide poisoning in the pathogenesis of konzo, malnutrition may be a key factor for the disease occurrence.

Xpert Mycobacterium tuberculosis/Rifampicin-Detected Rifampicin Resistance is a Suboptimal Surrogate for Multidrug-resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications.

BACKGROUND: Rifampicin (RIF) resistance is highly correlated with isoniazid (INH) resistance and used as proxy for multidrug-resistant tuberculosis (MDR-TB). Using MTBDRplus as a comparator, we evaluated the predictive value of Xpert MTB/RIF (Xpert)-detected RIF resistance for MDR-TB in eastern Democratic Republic of the Congo (DRC). METHODS: We conducted a cross-sectional study involving data from new or retreatment pulmonary adult TB cases evaluated between July 2013 and December 2016. Separate, paired sputa for smear microscopy and MTBDRplus were collected. Xpert testing was performed subject to the availability of Xpert cartridges on sample remnants after microscopy. RESULTS: Among 353 patients, 193 (54.7%) were previously treated and 224 (63.5%) were MTBDRplus TB positive. Of the 224, 43 (19.2%) were RIF monoresistant, 11 (4.9%) were INH monoresistant, 53 (23.7%) had MDR-TB, and 117 (52.2%) were RIF and INH susceptible. Overall, among the 96 samples detected by MTBDRplus as RIF resistant, 53 (55.2%) had MDR-TB. Xpert testing was performed in 179 (50.7%) specimens; among these, 163 (91.1%) were TB positive and 73 (44.8%) RIF resistant. Only 45/73 (61.6%) Xpert-identified RIF-resistant isolates had concomitant MTBDRplus-detected INH resistance. Xpert had a sensitivity of 100.0% (95% CI, 92.1-100.0) for detecting RIF resistance but a positive-predictive value of only 61.6% (95% CI, 49.5-72.8) for MDR-TB. The most frequent mutations associated with RIF and INH resistance were S531L and S315T1, respectively. CONCLUSIONS: In this high-risk MDR-TB study population, Xpert had low positive-predictive value for the presence of MDR-TB. Comprehensive resistance testing for both INH and RIF should be performed in this setting.

Micronutrient intake and prevalence of micronutrient inadequacy among women (15-49 y) and children (6-59 mo) in South Kivu and Kongo Central, Democratic Republic of the Congo (DRC).

Iron biofortified beans and carotenoid enriched cassava are proposed as a solution to combat iron and vitamin A deficiencies, respectively, in the Democratic Republic of Congo (DRC). To inform the need for biofortified foods, we conducted a survey in 2014 in two provinces of the DRC, South Kivu and Kongo Central. Unexpectedly, women of reproductive age (WRA; 15-49 y) and their children (6-59 m) had a low prevalence of biochemical iron and vitamin A deficiency, based on ferritin and retinol binding protein, respectively. To better understand the lack of biochemical deficiency of these nutrients, we examined the prevalence of inadequate intake for these and other select nutrients. Dietary intake was assessed using 24-hour recalls among 744 mother-child dyads. Repeat recalls on a non-consecutive day were conducted with a subsample of the study population to account for intra-individual variation and estimate usual intake. In WRA, the prevalence of inadequate iron intakes were 33% and 29% in South Kivu and Kongo Central, respecitvely. The prevalence of inadequate vitamin A intakes among WRA was low in South Kivu (18%) and negligible in Kongo Central (1%). Iron inadequacy was highest in infants (6-11 m) at 82% and 64% in South Kivu and Kongo Central, respectively. Among older children (12-59 m) in both provinces, the prevalence of iron inadequacy was similar at ~20%. There was a high prevalence of inadequate zinc intake in women and children (i.e. 79-86% among WRA and 56-91% among children 6-59 m) consistent with our findings of a high prevalence of low serum zinc in the same sample. Dietary data here corroborate the low prevalence of biochemical vitamin A deficiency but not iron. However, any change to the supply of red palm oil (primary source of vitamin A) would dramatically reduce population vitamin A intakes, thus a carotenoid enriched cassava program may be beneficial as a safety net measure. Crops biofortified with zinc also appear warranted. We caution that our findings cannot be extrapolated to the entire Congo where diverse agro-ecological landscape exist or when political and environmental shocks occur which challenge food production.

Seroprevalence of Zika virus in selected regions in Kenya.

BACKGROUND: The Zika virus pandemic in South America in 2015-2016 and the association of Zika virus infection with neurological complications such as microcephaly in newborns distressed the global community. There is limited data on the prevalence of Zika virus in Kenya despite evidence of its circulation in East Africa. This study aimed at assessing the seroprevalence of Zika virus in selected areas in Kenya. METHODS: Healthy adult human sera originally collected from Nairobi, Eldoret and Kisumu from 2009 to 2014 and archived at the University of Nairobi laboratories were examined for Zika virus antibodies. An IgG-based ELISA was used to screen 577 sera. Any serum tested positive by ELISA was confirmed for Zika virus infection by plaque reduction neutralization test (PRNT). RESULTS: The seroprevalence of Zika virus in the study population was about 0.2 % (1/577) as confirmed by PRNT. Additionally, three sera that were false positive by ELISA for Zika virus were confirmed as positive for dengue virus by PRNT. CONCLUSION: There was evidence of low previous exposure to Zika virus in the study population. Of the three regions in Kenya where sera for this study were obtained, only Kisumu County had one case of previous exposure to Zika virus.

Prevention against malaria before the first antenatal visit and absence of anaemia at the first visit were protective from low birth weight: results from a South Kivu cohort, Democratic Republic of the Congo.

Background: There is little information on the causes of low birth weight (LBW, <2500 g) in South Kivu. The authors determined the prevalence of LBW among full-term newborns, and its relationship with malaria and anaemia at the first antenatal visit (ANV1) in the rural health zone of Miti-Murhesa, in the eastern Democratic Republic of the Congo. Methods: Four-hundred-and-seventy-eight pregnant women in the second trimester attending their first antenatal clinic were recruited between November 2010 and July 2011, and followed-up until delivery. Besides information on use of preventive measures and malaria morbidity, anthropometric measures and a blood sample were collected. Results: Women's mean age (SD) at enrolment, was 26 (6.5) years (n=434); prevalence of malaria was 9.5% (43/453) and that of anaemia 32.2% (141/439). The latter was significantly more frequent in malaria-infected women and in those who had not been dewormed. At delivery, prevalence of LBW was 6.5% (23/355) and was independently associated with not sleeping under insecticide-treated bed net (p=0.030), mother's height <150 cm (p=0.001) and anaemia at the ANV1 (p=0.006). Conclusion: In South Kivu, malaria and anaemia are important risk factors for LBW, and should be prevented among all women of reproductive age.

Malaria and Iron Load at the First Antenatal Visit in the Rural South Kivu, Democratic Republic of the Congo: Is Iron Supplementation Safe or Could It Be Harmful?

We investigated the relationship between malaria infection and iron status in 531 pregnant women in South Kivu, Democratic Republic of the Congo. Sociodemographic data, information on morbidity, and clinical data were collected. A blood sample was collected at the first antenatal visit to diagnose malaria and measure serum ferritin (SF), soluble transferrin receptor, C-reactive protein, and α1-acid-glycoprotein. Malaria prevalence was 7.5%. Median (interquartile range) SF (adjusted for inflammation) was significantly higher in malaria-infected (82.9 µg/L [56.3-130.4]) than in non-infected (39.8 µg/L [23.6-60.8]) women (P < 0.001). Similarly, estimated mean body iron store was higher in malaria-infected women (P < 0.001). Malaria was significantly and independently associated with high levels of SF. Efforts to improve malaria prevention while correcting iron deficiency and anemia during pregnancy are warranted.

Malaria Is More Prevalent Than Iron Deficiency among Anemic Pregnant Women at the First Antenatal Visit in Rural South Kivu.

Anemia is common during pregnancy and is associated with poor outcomes. Objectives were not only 1) to determine the prevalence of anemia and iron deficiency (ID) but also 2) to identify other factors associated with anemia in pregnant women from South Kivu province, in the eastern Democratic Republic of Congo. Between December 2013 and March 2014, 531 women attending the first antenatal visit in their second trimester of pregnancy were recruited. Sociodemographic, clinical, and biological data were collected. Hemoglobin (Hb) was determined by a portable photometer (Hemocue® Hb201+), and anemia was defined as altitude-adjusted Hb < 110 g/L. ID was defined as serum ferritin < 15 µg/L adjusted for inflammation status (C-reactive protein [CRP] > 5 mg/L and/or α-1-acid glycoprotein > 1 g/L) whereas hypoalbuminemia was defined as serum albumin < 35 g/L. A Giemsa-stained blood smear was used to diagnose malaria. The median age (interquartile range ) was 25.5 (21.1-31.3) years, with anemia in 17.6% and ID in 8%. Malaria was present in 7.5% and hypoalbuminemia among 44%. Soluble transferrin receptor concentration was higher in the presence of inflammation and/or malaria. In the final logistic regression model, factors independently associated with anemia were malaria (adjusted odds ratio [aOR]: 11.24 (4.98-25.37) P < 0.001), hypoalbuminemia [aOR: 2.14 (1.27-3.59); P = 0.004] and elevated CRP [aOR: 1.94 (1.10-3.45); P = 0.022]. ID was not highly prevalent and not associated with anemia in our population. Effective control of anemia during pregnancy in this region should consider fighting malaria and other infectious diseases in combination with measures to improve women's nutrition, both before and during pregnancy.

High Prevalence of Anemia but Low Level of Iron Deficiency in Preschool Children during a Low Transmission Period of Malaria in Rural Kivu, Democratic Republic of the Congo.

Anemia is a worldwide public health concern especially in preschool children in developing countries and iron deficiency (ID) is generally assumed to cause at least 50% of the cases. However, data on this contribution are scarce. To close this gap, we determined in 2013 the contribution of ID in the etiology of anemia and measured others factors associated to noniron deficiency anemia (NIDA) in 900 preschool children randomly selected during a two-stage cluster nutritional survey in the Miti-Murhesa health zone, in eastern Democratic Republic of the Congo. In these children, we collected sociodemographic, clinical, and biological parameters and determined the nutritional status according to the World Health Organization 2006 standards. Anemia was defined as altitude-adjusted hemoglobin < 110 g/L and ID was defined as serum ferritin < 12 µg/L or < 30 µg/L in the absence or presence of inflammation, respectively. Median (interquartile range) age was 29.4 (12-45) months. The prevalence of anemia was 46.6% (391/838) among whom only 16.5% (62/377) had ID. Among children without signs of inflammation, only 4.4% (11/251) met the ferritin-based (unadjusted) definition of ID. Logistic regression analysis identified ID, history of fever during the last 2 weeks and mid-upper arm circumference < 125 mm as the only independent factors associated to anemia. In conclusion, anemia is a severe public health problem in the Miti-Murhesa health zone, but NIDA is mostly predominant and needs to be further studied. Control of infections and prevention of acute undernutrition (wasting) are some of appropriate interventions to reduce the burden anemia in this region.

Serum Soluble Transferrin Receptor Concentrations Are Elevated in Congolese Children with Glucose-6-Phosphate Dehydrogenase Variants, but Not Sickle Cell Variants or α-Thalassemia.

Background: Anemia is common in Congolese children, and inherited blood disorders may be a contributing cause. The presence of sickle cell variants, X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency and α-thalassemia, has been previously reported. G6PD A- deficiency is characterized by the co-inheritance of G6PD 376 and 202 variants and is common in sub-Saharan Africa.Objective: We aimed to measure the associations between inherited blood disorders and hemoglobin, ferritin, and soluble transferrin receptor (sTfR) concentrations in Congolese children.Methods: Venous blood was collected from 744 children aged 6-59 mo from 2 provinces. We measured biomarkers of nutritional and inflammation status and malaria. Pyrosequencing was used to detect sickle cell variants. Polymerase chain reaction was used to detect G6PD variants and α-thalassemia deletions.Results: Overall, 11% of children had a sickle cell variant, 19% of boys were G6PD A- hemizygotes, 12% and 10% of girls were G6PD A- hetero- or homozygotes, respectively, and 12% of children had α-thalassemia. Multivariable linear regression models (adjusted for age, province, altitude, malaria, and biomarkers of nutritional and inflammation status) showed that G6PD A- hemizygous boys and G6PD 376 homozygous girls had higher sTfR concentrations [geometric mean ratios (95% CIs): 1.20 (1.03, 1.39) and 1.25 (1.02, 1.53), respectively] than children with no G6PD variants. Hemoglobin and ferritin concentrations were not independently associated with any of the inherited blood disorder genotypes.Conclusions: We found that 2 G6PD variant genotypes were associated with elevated sTfR concentrations, which limits the accuracy of sTfR as a biomarker of iron status in this population.

Knowledge, Attitudes, and Practices of Health-Care Workers About Viral Hepatitis B and C in South Kivu.

Health-care workers (HCWs) are at risk of infections associated with accidental exposure to blood, including viral hepatitis B (HBV) and C (HCV). A survey using a questionnaire was conducted on 250 HCW in Bukavu, an eastern town of the Democratic Republic of Congo, to analyze their attitude and knowledge about these two viruses. A response rate of 86.8% (217/250) was obtained. The mean age of the respondents was 39.6 ± 9.8 years, in majority from paramedical staff (66.4%) and with more than 5 years of professional experience (60.8%). The mean proportion of adequate answers on HBV and HCV was 33.2% (±11%) and 30.6% (±7%), respectively. Ninety-three HCW (42.8%) reported recent experience of blood exposure accident, more frequently among the paramedical staff (50%) than physicians (28.8%; P = 0.002). This was mainly related to inadequate protection resources (76.9%). Among all participants, only 24.4% had a history of at least one injection of HBV vaccine; this was more frequently found among physicians than among paramedical staff (49.3% versus 11.8%; P < 0.001). Moreover, only 3.8% of vaccinated HCW received the complete vaccination schedule of three vaccine doses. The efficiency of this vaccine is not well recognized by HCW, and the majority of them seemed to be more worried about the risk of infection by human immunodeficiency virus than by viral hepatitis. Our study reveals that the level of knowledge about HBV and HCV is rather low among HCW in Bukavu.

Anemia and Micronutrient Status of Women of Childbearing Age and Children 6-59 Months in the Democratic Republic of the Congo.

Little is known about the micronutrient status of women and children in the Democratic Republic of the Congo, which is critical for the design of effective nutrition interventions. We recruited 744 mother-child pairs from South Kivu (SK) and Kongo Central (KC). We determined hemoglobin (Hb), serum zinc, vitamin B12, folate, ferritin, soluble transferrin receptor (sTfR), retinol binding protein (RBP), C-reactive protein, and α-1 acid glycoprotein concentrations. Anemia prevalence was determined using Hb adjusted for altitude alone and Hb adjusted for both altitude and ethnicity. Anemia prevalence was lower after Hb adjustment for altitude and ethnicity, compared to only altitude, among women (6% vs. 17% in SK; 10% vs. 32% in KC), children 6-23 months (26% vs. 59% in SK; 25% vs. 42% in KC), and children 24-59 months (14% vs. 35% in SK; 23% vs. 44% in KC), respectively. Iron deficiency was seemingly higher with sTfR as compared to inflammation-adjusted ferritin among women (18% vs. 4% in SK; 21% vs. 5% in KC), children 6-23 months (51% vs. 14% in SK; 74% vs. 10% in KC), and children 24-59 months (23% vs. 4% in SK; 58% vs. 1% in KC). Regardless of indicator, iron deficiency anemia (IDA) never exceeded 3% in women. In children, IDA reached almost 20% when sTfR was used but was only 10% with ferritin. Folate, B12, and vitamin A (RBP) deficiencies were all very low (<5%); RBP was 10% in children. The prevalence of anemia was unexpectedly low. Inflammation-adjusted zinc deficiency was high among women (52% in SK; 58% in KC), children 6-23 months (23% in SK; 20% in KC), and children 24-59 months (25% in SK; 27% in KC). The rate of biochemical zinc deficiency among Congolese women and children requires attention.