A genomic appraisal of invasive Salmonella Typhimurium and associated antibiotic resistance in sub-Saharan Africa.

Invasive non-typhoidal Salmonella (iNTS) disease manifesting as bloodstream infection with high mortality is responsible for a huge public health burden in sub-Saharan Africa. Salmonella enterica serovar Typhimurium (S. Typhimurium) is the main cause of iNTS disease in Africa. By analysing whole genome sequence data from 1303 S. Typhimurium isolates originating from 19 African countries and isolated between 1979 and 2017, here we show a thorough scaled appraisal of the population structure of iNTS disease caused by S. Typhimurium across many of Africa's most impacted countries. At least six invasive S. Typhimurium clades have already emerged, with ST313 lineage 2 or ST313-L2 driving the current pandemic. ST313-L2 likely emerged in the Democratic Republic of Congo around 1980 and further spread in the mid 1990s. We observed plasmid-borne as well as chromosomally encoded fluoroquinolone resistance underlying emergences of extensive-drug and pan-drug resistance. Our work provides an overview of the evolution of invasive S. Typhimurium disease, and can be exploited to target control measures.

Molecular characterization of Streptococcus pneumoniae causing disease among children in Nigeria during the introduction of PCV10 (GSK).

Streptococcus pneumoniae (pneumococcus) is a leading vaccine-preventable cause of childhood invasive disease. Nigeria has the second highest pneumococcal disease burden globally, with an estimated ~49 000 child deaths caused by pneumococcal infections each year. Ten-valent pneumococcal conjugate vaccine (GSK; PCV10) was introduced in December 2014 in a phased approach. However, few studies have characterized the disease-causing pneumococci from Nigeria. This study assessed the prevalence of serotypes, antibiotic susceptibility and genomic lineages using whole genome sequencing and identified lineages that could potentially escape PCV10 (GSK). We also investigated the potential differences in pneumococcal lineage features between children with and without sickle cell disease. A collection of 192 disease-causing pneumococcal isolates was obtained from Kano (n=189) and Abuja (n=3) states, Nigeria, between 1 January 2014 and 31 May 2018. The majority (99 %, 190/192) of specimens were recovered from children aged 5 years or under. Among them, 37 children had confirmed or traits of sickle cell disease. Our findings identified 25 serotypes expressed by 43 Global Pneumococcal Sequence Clusters (GPSCs) and 85 sequence types (STs). The most common serotypes were 14 (18 %, n=35), 6B (16 %, n=31), 1 (9 %, n=17), 5 (9 %, n=17) and 6A (9 %, n=17); all except serotype 6A are included in PCV10 (GSK). PCV10 (SII; PNEUMOSIL) and PCV13 formulations include serotypes 6A and 19A which would increase the overall coverage from 67 % by PCV10 (GSK) to 78 and 82 %, respectively. The pneumococcal lineages were a mix of globally spreading and unique local lineages. Following the use of PCV10 (GSK), GPSC5 expressing serotype 6A, GPSC10 (19A), GPSC26 (12F and 46) and GPSC627 (9L) are non-vaccine type lineages that could persist and potentially expand under vaccine-selective pressure. Approximately half (52 %, 99/192) of the pneumococcal isolates were resistant to the first-line antibiotic penicillin and 44 % (85/192) were multidrug-resistant. Erythromycin resistance was very low (2 %, 3/192). There was no significant difference in clinical manifestation, serotype prevalence or antibiotic resistance between children with and without traits of or confirmed sickle cell disease. In summary, our findings show that a high percentage of the pneumococcal disease were caused by the serotypes that are covered by currently available vaccines. Given the low prevalence of resistance, macrolide antibiotics, such as erythromycin, should be considered as an option to treat pneumococcal disease in Nigeria. However, appropriate use of macrolide antibiotics should be vigilantly monitored to prevent the potential increase in macrolide resistance.

Correlate of Left Ventricular Systolic Function in Children with Human Immunodeficiency Virus Infection on Combined Highly Active Antiretroviral Medications in Aminu Kano Teaching Hospital, Kano State.

Background: Human immunodeficiency virus (HIV) affects many organ systems in the body including the cardiovascular system, often manifesting as a subclinical left ventricular (LV) systolic dysfunction that may progress to heart failure. Aim: This study assessed the prevalence of LV systolic dysfunction in children on highly active antiretroviral therapy (HAART) with established clinical stage 1 HIV-disease. Materials and Methods: The study was a cross-sectional comparative study conducted in Aminu Kano Teaching Hospital from April to August 2019 on 200. It involved study participants comprising 100 WHO clinical stage 1 HIV-infected children and 100 control subjects, aged between 1 and 18 years selected using systematic sampling method. Echocardiography was carried out on the study participants who had already completed a pretested questionnaire. Results: Out of 100 HIV-infected children studied, 49 were males and 51 females (Male: Female ratio; 0.96:1.0). The mean age at diagnosis of HIV infection was 2.6 (±2.6 years) and the median viral load was 35 copies/ml. The mean ejection and shortening fractions in HIV-infected children were 59.0% and 31.0%, respectively, compared to 64.4% and 34.0% in control subjects, respectively, and were statistically significant (P = 0.000). The prevalence of LV systolic dysfunction was 8.0% (8 out of 100) in HIV-infected children while the control groups had zero prevalence (P = 0.002). The age at diagnosis correlated negatively with LV systolic dysfunction (r = 0.23, P = 0.02). Conclusion: This study found a subclinical LV systolic dysfunction in an HAART-established clinical stage 1 HIV-infected children. The age at diagnosis was negatively correlated with the LV systolic function. This study, therefore, support the inclusion of routine echocardiography into the evaluation of HIV-infected children.

Nasal carriage of meticillin-resistant Staphylococcus aureus among children living with HIV attending Infectious Diseases Clinics in Kano, Nigeria.

Background: Children living with HIV (CLWH) are at risk of colonisation and infection with meticillin-resistant Staphylococcus aureus (MRSA). All S. aureus isolates from CLWH with bloodstream infections in Kano were MRSA. Aim: To estimate the prevalence of nasal colonisation with S. aureus and MRSA in CLWH in Kano State and to determine associated risk factors. Methods: A cross-sectional study was performed in the infectious diseases clinics of two public hospitals in Kano involving 214 CLWH/caregiver pairs. Children were selected from clinic registers by simple random sampling and an interviewer-administered questionnaire used to elicit factors associated with MRSA carriage from the caregivers. Clinical records were reviewed for patients' medical histories. Standard laboratory techniques were used to isolate S. aureus from nasal swabs collected from CLWH. MRSA was detected using the cefoxitin disc diffusion method and PCR for mecA gene detection. We measured the prevalence of S. aureus and MRSA carriage in the CLWH and calculated adjusted odds ratios (AOR) for factors associated with MRSA. Results: Nasal S. aureus carriage in CLWH was 18.7% (40/214). Cefoxitin disc diffusion identified 6/214 (2.8%) of CLWH were MRSA carriers, while PCR identified that 9/214 (4.2%) of CLWH were MRSA carriers. Recent hospitalisation (AOR: 61.04; 95% CI: 9.01-413.38) and recent antibiotic therapy (AOR: 7.52; 95% CI: 1.07-52.95) were independent risk factors for MRSA colonisation. Conclusions: The rate of MRSA nasal colonisation among CLWH in Kano was similar to that reported in other studies in Africa. Infection prevention and control measures including MRSA screening and decolonisation, as well as education for CLWH and their carers should be introduced to reduce MRSA spread.

Effects of prenatal exposure to maternal COVID-19 and perinatal care on neonatal outcome: results from the INTERCOVID Multinational Cohort Study.

BACKGROUND: The effect of COVID-19 in pregnancy on maternal outcomes and its association with preeclampsia and gestational diabetes mellitus have been reported; however, a detailed understanding of the effects of maternal positivity, delivery mode, and perinatal practices on fetal and neonatal outcomes is urgently needed. OBJECTIVE: To evaluate the impact of COVID-19 on fetal and neonatal outcomes and the role of mode of delivery, breastfeeding, and early neonatal care practices on the risk of mother-to-child transmission. STUDY DESIGN: In this cohort study that took place from March 2020 to March 2021, involving 43 institutions in 18 countries, 2 unmatched, consecutive, unexposed women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. COVID-19 in pregnancy was determined by laboratory confirmation and/or radiological pulmonary findings or ≥2 predefined COVID-19 symptoms. The outcome measures were indices of neonatal and perinatal morbidity and mortality, neonatal positivity and its correlation with mode of delivery, breastfeeding, and hospital neonatal care practices. RESULTS: A total of 586 neonates born to women with COVID-19 diagnosis and 1535 neonates born to women without COVID-19 diagnosis were enrolled. Women with COVID-19 diagnosis had a higher rate of cesarean delivery (52.8% vs 38.5% for those without COVID-19 diagnosis, P<.01) and pregnancy-related complications, such as hypertensive disorders of pregnancy and fetal distress (all with P<.001), than women without COVID-19 diagnosis. Maternal diagnosis of COVID-19 carried an increased rate of preterm birth (P≤.001) and lower neonatal weight (P≤.001), length, and head circumference at birth. In mothers with COVID-19 diagnosis, the length of in utero exposure was significantly correlated to the risk of the neonate testing positive (odds ratio, 4.5; 95% confidence interval, 2.2-9.4 for length of in utero exposure >14 days). Among neonates born to mothers with COVID-19 diagnosis, birth via cesarean delivery was a risk factor for testing positive for COVID-19 (odds ratio, 2.4; 95% confidence interval, 1.2-4.7), even when severity of maternal conditions was considered and after multivariable logistic analysis. In the subgroup of neonates born to women with COVID-19 diagnosis, the outcomes worsened when the neonate also tested positive, with higher rates of neonatal intensive care unit admission, fever, gastrointestinal and respiratory symptoms, and death, even after adjusting for prematurity. Breastfeeding by mothers with COVID-19 diagnosis and hospital neonatal care practices, including immediate skin-to-skin contact and rooming-in, were not associated with an increased risk of newborn positivity. CONCLUSION: In this multinational cohort study, COVID-19 in pregnancy was associated with increased maternal and neonatal complications. Cesarean delivery was significantly associated with newborn COVID-19 diagnosis. Vaginal delivery should be considered the safest mode of delivery if obstetrical and health conditions allow it. Mother-to-child skin-to-skin contact, rooming-in, and direct breastfeeding were not risk factors for newborn COVID-19 diagnosis, thus well-established best practices can be continued among women with COVID-19 diagnosis.

Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study.

BACKGROUND: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. OBJECTIVE: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. STUDY DESIGN: This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. RESULTS: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32-2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25-2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17-3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99-2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99-5.49) and 6.26 (95% confidence interval, 4.35-9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63-2.86; risk ratio, 2.53; 95% confidence interval, 1.44-4.45; and risk ratio, 2.84; 95% confidence interval, 1.67-4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32-2.35), 2.07 (95% confidence interval, 1.20-3.57), and 2.77 (95% confidence interval, 1.66-4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. CONCLUSION: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19.

Correlates of Health Care Workers' Knowledge and HIV-Exposed Infant Immunization Counseling Practice in Northern Nigeria.

BACKGROUND: Human Immunodeficiency Virus (HIV)-exposed and HIV-infected infants are at increased risk of vaccine-preventable diseases. However, little is known about health care workers' knowledge and immunization counseling practices in this population. We determined the predictors of health care workers' knowledge of vertical transmission risks, HIV exposed/infected infant immunization, and counseling practices in a tertiary center in Northern Nigeria. METHODS: A cross-section of 297 health workers were interviewed using a structured, validated questionnaire. Knowledge and HIV-exposed infant immunization counseling practices were analyzed, and adjusted odds ratios for predictors were derived from logistic regression models. RESULTS: Of the 297 participating health care workers, (32.3%, n=96) had adequate knowledge of HIV-exposed/infected infant immunization. Two-thirds (67%, n=199) of the participants appropriately identified the timing of infant diagnosis, while (73%, n=217) and (56.2%, n=167) correctly categorized infants as HIV-exposed and HIV-infected, respectively. Only (19.5%, n=58) participants had ever counselled a HIV-positive mother on infant immunization. Knowledge was predicted by work unit (HIV clinic vs. Obstetrics & Gynecology clinic), (Adjusted Odds Ratio (AOR) =3.78, 95% CI: 1.27-5.54), age (30-39 vs. <30 years), (AOR=2.24, 95% CI:1.19-5.67), years of experience (≥10 vs. <5), (AOR=1.76, 95% CI: 1.15-6.04), number of children (1 vs. 0), (AOR=1.73, 95% CI:1.14-4.23), infant immunization training (yes vs. no), (AOR=1.57, 95% CI:1.12-5.43), female sex (AOR = 1.17, 95% CI:1.06-2.21), profession (nurse/midwife vs. physician), (AOR=0.44, 95% CI:0.21-0.94) and previous HIV test (no vs. yes), (AOR=0.67, 95% CI:0.21-0.83). CONCLUSION AND GLOBAL HEALTH IMPLICATIONS: Knowledge of HIV-exposed infant immunization was low and counseling practices were sub-optimal. Both immunization knowledge and counseling practices were predicted by demographic, professional, and training variables. Our findings indicate the need for educating health care workers on HIV exposed/infected infant immunization policy and improving counseling skills through capacity-building programs.

A Prospective Cohort Study of the Clinical Predictors of Bacteremia in Under-Five Children With Acute Undifferentiated Fever Attending a Secondary Health Facility in Northwestern Nigeria.

BACKGROUND: Children with acute febrile illness with no localizing signs often receive antibiotics empirically in most resource-poor settings. However, little is known about the burden of bacteremia in this category of patients, and an appraisal is thus warranted. This will guide clinical practice and promote rational antibiotics use. METHODS: We prospectively followed up 140 under-five children who presented with acute undifferentiated fever at the emergency/outpatient pediatric unit of a secondary healthcare facility. Baseline clinical and laboratory information was obtained and documented in a structured questionnaire. We compared baseline characteristics between participants with bacteremia and those without bacteremia. We further fitted a multivariable logistic regression model to identify factors predictive of bacteremia among the cohort. RESULT: The prevalence of bacteremia was 17.1%, and Salmonella Typhi was the most frequently (40.9%) isolated pathogen. The majority (78.6%) of the study participants were managed as outpatients. The participants who required admission were four times more likely to have bacteremia when compared to those managed as outpatients (AOR 4.08, 95% CI 1.19 to 14.00). There is a four times likelihood of bacteremia (AOR 4.75, 95% CI 1.48 to 15.29) with a fever duration of beyond 7 days. Similarly, participants who were admitted with lethargy were six times more likely to have bacteremia (AOR 6.20, 95% CI 1.15 to 33.44). Other significant predictors were tachypnea and lymphopenia. CONCLUSION: Among under-five children with acute undifferentiated fever, longer duration of fever, lethargy, inpatient care, tachypnea, and lymphopenia were the significant predictors of bacteremia.

A cross-sectional study of prevalence and risk factors for stunting among under-fives attending acute malnutrition treatment programmes in north-western Nigeria: Should these programmes be adapted to also manage stunting?

BACKGROUND: Stunting and severe wasting can co-occur in under-fives, predisposing them to increased risks for morbidity and mortality. The Community Management of Acute Malnutrition (CMAM) programme, which provides outpatient malnutrition care for severely wasted children, has been successful at managing severe wasting, but there are limited data on stunting among entrants into these programmes. METHODS: We performed secondary analysis of data collected from attendees of two CMAM centres in north-western Nigeria. Using WHO reference standards, we determined the prevalence of concurrent stunting (height/length-for-age <-2 SD) among severely wasted children (weight-for-height z-scores <-3 SD). We identified individual and household-level risk factors for concurrent stunting using multivariable logistic regression analysis. RESULTS: Our cohort comprised 472 severely wasted children and the majority (82.8%) were stunted. Age groups of 12-23 mo (adjusted OR [AOR]=2.38, 95% CI 1.26 to 4.48) and 24-35 mo (AOR=7.81, 95% CI 1.99 to 30.67), male gender (AOR=2.51, 95% CI 1.43 to 4.39) and attending the rural malnutrition clinic (AOR=3.08, 95% CI 1.64 to 5.79) were associated with a significantly increased probability of stunting. CONCLUSIONS: Stunting prevalence is high among severely wasted children attending CMAM programmes in north-western Nigeria. Policymakers need to adapt these treatment programmes to also cater for stunting, taking into account practical programmatic realities such as available expertise and scarce resource allocation.

Molecular characterization of invasive Enterobacteriaceae from pediatric patients in Central and Northwestern Nigeria.

BACKGROUND: Bacteremia is a leading cause of mortality in developing countries, however, etiologic evaluation is infrequent and empiric antibiotic use not evidence-based. Here, we evaluated the patterns of ESBL resistance in children enrolled into a surveillance study for community acquired bacteremic syndromes across health facilities in Central and Northwestern Nigeria. METHOD: Blood culture was performed for children aged less than 5 years suspected of having sepsis from Sept 2008-Dec 2016. Blood was incubated using the BACTEC00AE system and Enterobacteriacea identified to the species level using Analytical Profile Index (API20E®). Antibiotic susceptibility profile was determined by the disc diffusion method. Real time PCR was used to characterize genes responsible for ESBL production. RESULT: Of 21,000 children screened from Sept 2008-Dec 2016, 2,625(12.5%) were culture-positive. A total of 413 Enterobacteriaceae available for analysis were screened for ESBL. ESBL production was detected in 160 Enterobacteriaceae, high resistance rates were observed among ESBL-positive isolates for Ceftriaxone (92.3%), Aztreonam (96.8%), Cefpodoxime (96.3%), Cefotaxime (98.8%) and Trimethoprim/sulfamethoxazole (90%), while 87.5%, 90.7%, and 91.9% of the isolates were susceptible to Imipenem, Amikacin and Meropenem respectively. Frequently detected resistance genes were blaTEM-83.8% (134/160), and, blaCTX-M 83.1% (133/160) followed by blaSHVgenes 66.3% (106/160). Co-existence of blaCTX-M, blaTEM and blaSHV was seen in 94/160 (58.8%), blaCTX-M and blaTEM in 118/160 (73.8%), blaTEM and blaSHV in 97/160 (60.6%) and blaCTX-M and blaSHV in 100/160 (62.5%) of isolates tested. CONCLUSION: Our results indicate a high prevalence of bacteremia from ESBL Enterobacteriaceae in this population of children. These are resistant to commonly used antibiotics and careful choice of antibiotic treatment options is critical. Further studies to evaluate transmission dynamics of resistance genes could help in the reduction of ESBL resistance in these settings.

Socio-demographic and Household-Level Risk Factors for Severe Acute Malnutrition in Pre-school Children in North-Western Nigeria.

BACKGROUND: Severe acute malnutrition (SAM) is associated with significant morbidity and mortality and is disproportionately distributed mainly in developing countries. In Nigeria, the prevalence of SAM in the North-Western region of the country is significantly higher than the national average. In this study, we identified risk factors for SAM in North-Western Nigeria. Identifying such risk factors would be helpful in developing local preventive strategies and providing insights for broader SAM control programs in other high-burden country settings. METHODS: We performed post hoc data analysis, comparing baseline socio-demographic and household-level risk factors in a cohort of 1011 children aged between 6 and 59 months who either had SAM or were well-nourished children. We defined nutritional status using the World Health Organization (WHO) reference standards and investigated the association between SAM and our identified risk factors using multivariable logistic regression model. RESULTS: Children aged between 12 and 23 months [adjusted odds ratio (AOR) 2.95, 95% confidence interval (CI) 1.99-4.38], household who reared domestic animals (AOR 1.94, 95% CI 1.40-2.69) and those from polygamous households (AOR 1.91, 95% CI 1.33-2.74) had significantly increased odds of developing SAM. Parental education and being on the household diet reduced the odds of having SAM. CONCLUSIONS: Our findings suggest the need to develop optimal complementary feeding nutrition programs and promote adult and general education in our community. Cultural and feeding practices in local polygamous households also need further investigation to understand the association between polygamy with SAM.

Paper-based microchip electrophoresis for point-of-care hemoglobin testing.

Nearly 7% of the world's population live with a hemoglobin variant. Hemoglobins S, C, and E are the most common and significant hemoglobin variants worldwide. Sickle cell disease, caused by hemoglobin S, is highly prevalent in sub-Saharan Africa and in tribal populations of Central India. Hemoglobin C is common in West Africa, and hemoglobin E is common in Southeast Asia. Screening for significant hemoglobin disorders is not currently feasible in many low-income countries with the high disease burden. Lack of early diagnosis leads to preventable high morbidity and mortality in children born with hemoglobin variants in low-resource settings. Here, we describe HemeChip, the first miniaturized, paper-based, microchip electrophoresis platform for identifying the most common hemoglobin variants easily and affordably at the point-of-care in low-resource settings. HemeChip test works with a drop of blood. HemeChip system guides the user step-by-step through the test procedure with animated on-screen instructions. Hemoglobin identification and quantification is automatically performed, and hemoglobin types and percentages are displayed in an easily understandable, objective way. We show the feasibility and high accuracy of HemeChip via testing 768 subjects by clinical sites in the United States, Central India, sub-Saharan Africa, and Southeast Asia. Validation studies include hemoglobin E testing in Bangkok, Thailand, and hemoglobin S testing in Chhattisgarh, India, and in Kano, Nigeria, where the sickle cell disease burden is the highest in the world. Tests were performed by local users, including healthcare workers and clinical laboratory personnel. Study design, methods, and results are presented according to the Standards for Reporting Diagnostic Accuracy (STARD). HemeChip correctly identified all subjects with hemoglobin S, C, and E variants with 100% sensitivity, and displayed an overall diagnostic accuracy of 98.4% in comparison to reference standard methods. HemeChip is a versatile, mass-producible microchip electrophoresis platform that addresses a major unmet need of decentralized hemoglobin analysis in resource-limited settings.

A comparative cross-sectional study of prevalence and intensity of soil-transmitted helminthic infection between healthy and severe acutely malnourished pre-school aged children in Kano, Northern Nigeria.

BACKGROUND: Soil-transmitted helminthic (STH) infections are common in Sub-Saharan Africa. One method used for control of these helminths is mass anti-helminthic administration in populations at risk of STH infections. In this regard, empiric treatment of children with Severe Acute Malnutrition (SAM) for STH infection is practiced in this region. It is however unclear if children with SAM suffer more from STH infection than healthy children. The objective of this study was to compare prevalence and intensity of STH infection between pre-school aged children with SAM and healthy children. METHODS: We approached 1114 pre-school aged children attending care in two health facilities in Kano, Nigeria to partake in this study. Of this number, we recruited 620 (55.7%) children, comprising 310 well-nourished children from well-baby clinics and 310 children with SAM from Community Management for Acute Malnutrition (CMAM) centres in these facilities. We assessed their nutritional status using World Health Organisation (WHO) growth charts and collected stool samples which we analysed using Formal-Ether Concentration technique to identify STH infection and Stoll's technique to assess intensities of STH infection. We fitted a logistic regression model to determine if there was any association between nutrition status and helminthic infection, adjusting for the confounding effects of socio-economic status and age. We compared intensity of STH infection (measured as eggs per gram of faeces) between both nutrition groups using the independent t-test. RESULTS: Overall STH prevalence in our population was low (2.7%) and we found no significant association between nutritional status and presence of STH infection (OR = 1.10, 95% CI 0.38 to 3.21). Majority of our study participants had either low or moderate (94.2%) and there was no statistically significant difference between intensity of STH infection (t value = - 1.52, P value = 0.13) in children with SAM and those who were well-nourished. CONCLUSIONS: The overall STH prevalence among pre-school children was low in Kano and we did not find prevalence and intensity of STH infection to differ significantly between preschool children with SAM and well-nourished children. Our findings confirm the WHO recommendation that at low levels of prevalence and intensity, interventions to control STH are unnecessary.

Detection of Streptococcus pneumoniae from culture-negative dried blood spots by real-time PCR in Nigerian children with acute febrile illness.

OBJECTIVES: Acute febrile illness is a common cause of hospital admission, and its associated infectious causes, of which a key bacterial causative agent is Streptococcus pneumoniae, contribute to substantial morbidity and mortality. We sought to evaluate the utility of real-time (rt)-PCR on dried blood spots (DBS) for diagnosis of S. pneumoniae in acute febrile illness among children presenting to hospitals in Nigeria. We previously described preliminary results in a sample of 537 patients. Here we present data from a larger collection of 1038 patients. RESULTS: Using rt-PCR for Streptococcus pneumoniae on 1038 dried blood spots from children prospectively enrolled with acute febrile illness, including 79 healthy controls, we detected pneumococcal DNA in nine of 15 blood culture-positive specimens, one culture-negative specimen from a high-risk group, a culture-confirmed non-pneumococcal specimen and a healthy control. Six culture-positive isolates (40%) were negative. Sensitivity was 60%, specificity 99.7%, positive predictive value 75% and negative predictive value 99.4%. Rt-PCR of DBS has limited sensitivity in blood specimens from acute febrile illness in children.

Development of ELISAs for diagnosis of acute typhoid fever in Nigerian children.

Improved serodiagnostic tests for typhoid fever (TF) are needed for surveillance, to facilitate patient management, curb antibiotic resistance, and inform public health programs. To address this need, IgA, IgM and IgG ELISAs using Salmonella enterica serovar Typhi (S. Typhi) lipopolysaccharide (LPS) and hemolysin E (t1477) protein were conducted on 86 Nigerian pediatric TF and 29 non-typhoidal Salmonella (NTS) cases, 178 culture-negative febrile cases, 28 "other" (i.e., non-Salmonella) pediatric infections, and 48 healthy Nigerian children. The best discrimination was achieved between TF and healthy children. LPS-specific IgA and IgM provided receiver operator characteristic areas under the curve (ROC AUC) values of 0.963 and 0.968, respectively, and 0.978 for IgA+M combined. Similar performance was achieved with t1477-specific IgA and IgM (0.968 and 0.968, respectively; 0.976 combined). IgG against LPS and t1477 was less accurate for discriminating these groups, possibly as a consequence of previous exposure, although ROC AUC values were still high (0.928 and 0.932, respectively). Importantly, discrimination between TF and children with other infections was maintained by LPS-specific IgA and IgM (AUC = 0.903 and 0.934, respectively; 0.938 combined), and slightly reduced for IgG (0.909), while t1477-specific IgG performed best (0.914). A similar pattern was seen when comparing TF with other infections from outside Nigeria. The t1477 may be recognized by cross-reactive antibodies from other acute infections, although a robust IgG response may provide some diagnostic utility in populations where incidence of other infections is low, such as in children. The data are consistent with IgA and IgM against S. Typhi LPS being specific markers of acute TF.

Caregiver satisfaction with paediatric HIV treatment and care in Nigeria and equity implications for children living with HIV.

Caregiver satisfaction has the potential to promote equity for children living with HIV, by influencing health-seeking behaviour. We measured dimensions of caregiver satisfaction with paediatric HIV treatment in Nigeria, and discuss its implications for equity by conducting facility-based exit interviews for caregivers of children receiving antiretroviral therapy in 20 purposively selected facilities within 5 geopolitical zones. Descriptive analysis and factor analysis were performed. Due to the hierarchical nature of the data, multilevel regression modelling was performed to investigate relationships between satisfaction factors and socio-demographic variables. Of 1550 caregivers interviewed, 63% (95% CI: 60.6-65.4) reported being very satisfied overall; however, satisfaction varied in some dimensions: only 55.6% (53.1-58.1) of caregivers could talk privately with health workers, 56.9% (54.4-59.3) reported that queues to see health workers were too long, and 89.9% (88.4-91.4) said that some health workers did not treat patients living with HIV with sufficient respect. Based on factor analysis, two underlying factors, labelled Availability and Attitude, were identified. In multilevel regression, the satisfaction with availability of services correlated with formal employment status (p < .01), whereas caregivers receiving care in private facilities were less likely satisfied with both availability (p < .01) and attitude of health workers (p < .05). State and facility levels influenced attitudes of the health workers (p < .01), but not availability of services. We conclude that high levels of overall satisfaction among caregivers masked dissatisfaction with some aspects of services. The two underlying satisfaction factors are part of access typology critical for closing equity gaps in access to HIV treatment between adults and children, and across socio-economic groups.

Molecular Detection of Streptococcus pneumoniae on Dried Blood Spots from Febrile Nigerian Children Compared to Culture.

BACKGROUND: Nigeria has one of the highest burdens of pneumococcal disease in the world, but accurate surveillance is lacking. Molecular detection of infectious pathogens in dried blood spots (DBS) is an ideal method for surveillance of infections in resource-limited settings because of its low cost, minimal blood volumes involved, and ease of storage at ambient temperature. Our study aim was to evaluate a Streptococcus pneumoniae real-time polymerase chain reaction (rt-PCR) assay on DBS from febrile Nigerian children on Whatman 903 and FTA filter papers, compared to the gold standard of culture. METHODS: Between September 2011 to May 2015, blood was collected from children 5 years of age or under who presented to six hospital study sites throughout northern and central Nigeria with febrile illness, and inoculated into blood culture bottles or spotted onto Whatman 903 or FTA filter paper. Culture and rt-PCR were performed on all samples. RESULTS: A total of 537 DBS specimens from 535 children were included in the study, of which 15 were culture-positive for S. pneumoniae. The rt-PCR assay detected S. pneumoniae in 12 DBS specimens (2.2%). One positive rt-PCR result was identified in a culture-negative specimen from a high-risk subject, and two positive rt-PCR results were negative on repeat testing. Six culture-confirmed cases of S. pneumoniae bacteremia were missed. Compared to culture, the overall sensitivities of Whatman 903 and FTA DBS for detection of S. pneumoniae were 57.1% (95% CI 18.4-90.1%) and 62.5% (95% CI 24.5-91.5%), respectively. Nonspecific amplification was noted in an additional 22 DBS (4.1%). Among these, six were positive for a non-S. pneumoniae pathogen on culture. CONCLUSIONS: Rt-PCR was able to detect S. pneumoniae from clinical DBS specimens, including from a culture-negative specimen. Our findings show promise of this approach as a surveillance diagnostic, but also raise important cautionary questions. Several DBS specimens were detected as S. pneumoniae by rt-PCR despite growth of a non-S. pneumoniae pathogen on culture. A precise definition of what constitutes a positive result is required to avoid falsely over-identifying specimens.

Salmonella Bacteremia Among Children in Central and Northwest Nigeria, 2008-2015.

BACKGROUND: Etiologic agents of childhood bacteremia remain poorly defined in Nigeria. The absence of such data promotes indiscriminate use of antibiotics and delays implementation of appropriate preventive strategies. METHODS: We established diagnostic laboratories for bacteremia surveillance at regional sites in central and northwest Nigeria. Acutely ill children aged <5 years with clinically suspected bacteremia were evaluated at rural and urban clinical facilities in the Federal Capital Territory, central region and in Kano, northwest Nigeria. Blood was cultured using the automated Bactec incubator system. RESULTS: Between September 2008 and April 2015, we screened 10,133 children. Clinically significant bacteremia was detected in 609 of 4051 (15%) in the northwest and 457 of 6082 (7.5%) in the central region. Across both regions, Salmonella species account for 24%-59.8% of bacteremias and are the commonest cause of childhood bacteremia, with a predominance of Salmonella enterica serovar Typhi. The prevalence of resistance to ampicillin, chloramphenicol, and cotrimoxazole was 38.11%, with regional differences in susceptibility to different antibiotics but high prevalence of resistance to readily available oral antibiotics. CONCLUSIONS: Salmonella Typhi is the leading cause of childhood bacteremia in central Nigeria. Expanded surveillance is planned to define the dynamics of transmission. The high prevalence of multidrug-resistant strains calls for improvement in environmental sanitation in the long term and vaccination in the short term.

Adherence to Artemisinin-Based Combination Therapy for the Treatment of Uncomplicated Malaria: A Systematic Review and Meta-Analysis.

Adherence to artemisinin-based combination therapy (ACT) is not clearly defined. This meta-analysis determines the prevalence and predictors of adherence to ACT. Twenty-five studies and six substudies met the inclusion criteria. The prevalence of ACT adherence in the public sector was significantly higher compared to retail sector (76% and 45%, resp., P < 0.0001). However, ACT adherence was similar across different ACT dosing regimens and formulations. In metaregression analysis prevalence estimates of adherence significantly decrease with increasing year of study publication (P = 0.046). Factors found to be significant predictors of ACT adherence were years of education ≥ 7 {odds ratio (OR) (95% CI) = 1.63 (1.05-2.53)}, higher income {2.0 (1.35-2.98)}, fatty food {4.6 (2.49-8.50)}, exact number of pills dispensed {4.09 (1.60-10.7)}, and belief in traditional medication for malaria {0.09 (0.01-0.78)}. The accuracy of pooled estimates could be limited by publication bias, and differing methods and thresholds of assessing adherence. To improve ACT adherence, educational programs to increase awareness and understanding of ACT dosing regimen are interventions urgently needed. Patients and caregivers should be provided with an adequate explanation at the time of prescribing and/or dispensing ACT.

Persistent microalbuminuria in human immunodeficiency virus infected children in kano, Nigeria.

Microalbuminuria has been reported to be a precursor of HIV related renal disease, which if detected early and coupled with appropriate intervention may slow or retard the progress of the disease. One hundred and seventy-eight HIV infected children aged 15 years and below were recruited from the Paediatric Infectious Disease Clinic of Aminu Kano Teaching Hospital (AKTH), Kano, to determine the prevalence of persistent microalbuminuria using the albumin creatinine ratio (ACR). Early morning urine samples and spot urine samples were analyzed using a dipstick specific for microalbumin. Those who tested positive had their samples reanalyzed in the laboratory using immunometric assay and Jaffe reaction method for albumin and creatinine, respectively. Patients that had ACR of 30-300 mg/g were said to have microalbuminuria and had their urine samples retested after 6 to 8 weeks. Twelve children (6.7%) had persistent microalbuminuria and had a mean age of 7.5 ± 3.3 years, with a male to female ratio of 1 : 1. There was no significant relationship between the finding of microalbuminuria and age, sex, duration of infection, and the use of highly active antiretroviral therapy. Periodic screening for microalbuminuria using albumin specific dipstick should be considered for children with HIV infection.