Search

Characterization of serological responses to Plasmodium falciparum (Pf) is of interest to understand disease burden and transmission dynamics; however, their interpretation is challenging. Dried blood spots from 30,815 participants aged 6 months to 15 years from the 2018 Nigeria HIV/AIDS Indicator and Impact Survey were analyzed by multiplex bead-based assay to measure immunoglobulin G (IgG) to Pf-stage-specific MSP-1, AMA-1, GLURPR0, LSA-1, and CSP. These IgG levels were analyzed by principal component analysis (PCA). PC1 and PC2 scores explained 41% and 17% of the total variance, respectively. PC1 unit vectors represented seropositivity. PC2 unit vectors for blood-stage antigens were in opposite directions to liver-stage and sporozoite antigens. PC2 scores were correlated with MSP-1 positively (R = 0.52, P < 0.001) and CSP negatively (R=-0.65, P < 0.001) and may help identify areas with prior exposure but higher risk for increased infections or epidemics. PCA of Pf serology can provide summary scores to possibly inform future programmatic interventions., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. CDC disclaimer: The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objectives: Evidence indicates that people living with HIV (PLHIV) are more impacted by COVID-19. The burden of SARS-CoV-2 infection among PLHIV is unknown in Nigeria., Methods: We conducted repeated cross-sectional SARS-CoV-2 serosurveys in 14 states and the Federal Capital Territory in Nigeria among PLHIV who had an HIV viral load (VL) test during April 2022 to January 2023. Evidence of SARS-CoV-2 immunoglobulin G (IgG) antibodies was assessed using a multiplex bead assay to measure IgG to spike (S), receptor binding domain (RBD), and nucleocapsid (N) proteins to identify potential infection and/or vaccination status., Results: Between April 2022 and January 2023, 47,614 remnant VL samples were included and tested for SARS-CoV-2 antibodies. Seroprevalence of SARS-CoV-2 infection, defined as IgG antibodies to spike and RBD591 [S+] and nucleocapsid [N+], (S+N+), ranged between 21.1% (95% confidence intervals [CI]: 11.4-31.8) in Ekiti State in January 2023 to 71.4% (95% CI 71.9-81.9) in Gombe State in November 2022, with overall steady trends within and between states over time, across age and sex., Conclusion: High rates of SARS-CoV-2 antibody seroprevalence among PLHIV in Nigeria were observed. This underscores the need to understand the association between HIV and SARS-CoV-2 to inform strategies to reduce the threat posed by COVID-19., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Published by Elsevier Ltd.)

Congenital transmission of Toxoplasma gondii can occur when a woman becomes infected for the first time during or just before pregnancy. Toxoplasma gondii in the fetus can lead to miscarriage, stillbirth, ocular or neurological abnormalities at birth, or progressive visual, hearing, motor, and cognitive deficiencies. The national seroprevalence of T. gondii infection in Nigeria was previously unknown. The 2018 Nigeria HIV/AIDS Indicator and Impact Survey collected demographic, socioeconomic, and HIV-related data and stored blood specimens with consent for future analysis for other pathogens of public health importance. We evaluated toxoplasmosis seropositivity and risk factors in a sample of 44,269 women of reproductive age (WRA) between 15 and 44 years. The national T. gondii seroprevalence among WRA was 26.8% (95% CI: 25.8-27.7%). We found that WRA from all 36 states and the Federal Capital Territory had T. gondii exposure. Seroprevalence was higher in 25- to 44-year-olds than in 15- to 24-year-olds. A similar proportion of pregnant and nonpregnant women were seropositive. Increased odds of seropositivity were associated with unimproved toilet facilities and drinking water sources, being in a higher wealth quintile, and primary and secondary education compared with no education. Decreased odds of seropositivity were associated with living in an urban area and owning livestock. This study provides the first-ever national seroprevalence estimate for WRA in Nigeria. Although information on known risk factors for toxoplasmosis (e.g., consumption of undercooked meat, cat ownership) was not collected, future studies could further investigate potential risk factors to inform the development of effective toxoplasmosis prevention measures.

Background: HIV testing remains an entry point into HIV care and treatment services. In 2007, Nigeria adopted and implemented a two-test rapid HIV testing algorithm of three HIV rapid test kits, following the sequence: Alere Determine (first test), Unigold TM (second test), and STAT-PAK ® as the tie-breaker. Sub-analysis of the 2018 Nigeria HIV/AIDS Indicator and Impact Survey data showed significant discordance between the first and second tests, necessitating an evaluation of the algorithm. This manuscript highlights lessons learnt from that evaluation., Intervention: A two-phased evaluation method was employed, including abstraction and analysis of retrospective HIV testing data from January 2017 to December 2019 from 24 selected sites supported by the United States President's Emergency Plan for AIDS Relief programme. A prospective evaluation of HIV testing was done among 2895 consecutively enrolled and consented adults, aged 15-64 years, accessing HIV testing services from three selected sites per state across the six geopolitical zones of Nigeria between July 2020 and September 2020. The prospective evaluation was performed both in the field and at the National Reference Laboratory under controlled laboratory conditions. Stakeholder engagements, strategic selection and training of study personnel, and integrated supportive supervision were employed to assure the quality of evaluation procedures and outcomes., Lessons Learnt: The algorithm showed higher sensitivity and specificity in the National Reference Laboratory compared with the field. The approaches to quality assurance were integral to the high-quality study outcomes., Recommendations: We recommend comparison of testing algorithms under evaluation against a gold standard., What This Study Adds: This study provides context-specific considerations in using World Health Organization recommendations to evaluate the Nigerian national HIV rapid testing algorithm., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

The first nationally representative, population-based study of schistosomiasis seroprevalence in Nigeria was conducted using blood samples and risk-factor data collected during the 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS). Schistosomiasis seroprevalence was estimated by analyzing samples for reactivity to schistosome soluble egg antigen (SEA) in a multiplex bead assay; NAIIS survey data were assessed to identify potential risk factors for seropositivity. The SEA antibody data were available for 31,459 children aged 0 to 14 years. Overall seroprevalence was 17.2% (95% CI: 16.3-18.1%). Seropositive children were identified in every age group, including children < 5 years, and seroprevalence increased with increasing age (P < 0.0001). Several factors were associated with increased odds of seropositivity, including being a boy (odds ratio [OR] = 1.34, 95% CI: 1.24-1.45), living in a rural area (OR = 2.2, 95% CI: 1.9-2.5), and animal ownership (OR = 1.67, 95% CI: 1.52-1.85). Access to improved sanitation and drinking water sources were associated with decreased odds of seropositivity (OR = 0.52, 95% CI: 0.47-0.58 and OR = 0.53, 95% CI: 0.47-0.60, respectively) regardless of whether the child lived in a rural (sanitation: adjusted odds ratio [aOR] = 0.7, 95% CI: 0.6-0.8; drinking water: aOR = 0.7, 95% CI: 0.6-0.8) or urban area (sanitation: aOR = 0.6, 95% CI: 0.5-0.7; drinking water: aOR = 0.5, 95% CI: 0.4-0.6), highlighting the importance of these factors for schistosomiasis prevention and control. These results identified additional risk populations (children < 5 years) and a new risk factor (animal ownership) and could be used to monitor the impact of control programs.

Background: Plasmodium falciparum malaria is a leading cause of child mortality in Nigeria. Neonates are born with maternal antibodies from placental transfer which may protect against malaria infection in the first months of life. The IgG dynamics of the transition from passively transferred antimalarial antibodies to actively acquired IgG from natural exposure have not been well elucidated., Methods: Blood samples collected during a 2018 Nigeria nationwide HIV/AIDS household survey were available for 9,443 children under 5 years of age, with a subset of infants under 2 months of age having maternal samples available (n=41). Samples were assayed for the P. falciparum HRP2 antigen and anti-malarial IgG antibodies. LOESS regression examined the dynamics in IgG response in the first 5 years of life. Correlation with maternal IgG levels was assessed for mother/child pairs., Results: Consistent decreases were observed in median IgG levels against all Plasmodium spp. antigen targets for the first months of life. At a population level, P. falciparum apical membrane antigen-1 (AMA1) and merozoite surface protein-1 19kD (PfMSP1) IgG decreased during the first 12 months of life before reaching a nadir, whereas IgGs to other targets only declined for the first 4 months of life. Seropositivity showed a similar decline with the lowest seropositivity against AMA1 and PfMSP1 at 10-12 months, though remaining above 50% during the first 2 years of life in higher transmission areas. No protective association was observed between IgG positivity and P. falciparum infection in infants. Maternal antibody levels showed a strong positive correlation with infant antibody levels for all P. falciparum antigens from birth to 2 months of age, but this correlation was lost by 6 months of age., Discussion: Maternally transferred anti-malarial IgG antibodies rapidly decline during the first 6 months of life, with variations among specific antigens and malaria transmission intensity. From 3-23 months of age, there was a wide range in IgG levels for the blood-stage antigens indicating high individual variation in antibody production as children are infected with malaria. Non- falciparum species-specific antigens showed similar patterns in waning immunity and correlation with paired mother's IgG levels compared to P. falciparum antigens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Leonard, Uhomoibhi, Abubakar, Ogunniyi, Mba, Greby, Okoye, Iriemenam, Ihekweazu, Steinhardt, Rogier and NMS4 Technical Working Group.)

Plasmodium falciparum (Pf) is the dominant malaria parasite in Nigeria though P. vivax (Pv), P. ovale (Po), and P. malariae (Pm) are also endemic. Blood samples (n = 31,234) were collected from children aged 0-14 years during a 2018 nationwide HIV survey and assayed for Plasmodium antigenemia, Plasmodium DNA, and IgG against Plasmodium MSP1-19 antigens. Of all children, 6.6% were estimated to have Pm infection and 1.4% Po infection with no Pv infections detected. The highest household wealth quintile was strongly protective against infection with Pm (aOR: 0.11, 95% CI: 0.05-0.22) or Po (aOR= 0.01, 0.00-0.10). Overall Pm seroprevalence was 34.2% (95% CI: 33.3-35.2) with lower estimates for Po (12.1%, 11.6-12.5) and Pv (6.3%, 6.0-6.7). Pm seropositivity was detected throughout the country with several local government areas showing >50% seroprevalence. Serological and DNA indicators show widespread exposure of Nigerian children to Pm with lower rates to Po and Pv., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Prevalence estimates are critical for malaria programming efforts but generating these from non-malaria surveys is not standard practice. Malaria prevalence estimates for 6-59-month-old Nigerian children were compared between two national household surveys performed simultaneously in 2018: a Demographic and Health Survey (DHS) and the Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS). DHS tested via microscopy (n = 8298) and HRP2-based rapid diagnostic test (RDT, n = 11,351), and NAIIS collected dried blood spots (DBS) which were later tested for histidine-rich protein 2 (HRP2) antigen (n = 8029). National Plasmodium falciparum prevalence was 22.6% (95% CI 21.2- 24.1%) via microscopy and 36.2% (34.6- 37.8%) via RDT according to DHS, and HRP2 antigenemia was 38.3% (36.7-39.9%) by NAIIS DBS. Between the two surveys, significant rank-order correlation occurred for state-level malaria prevalence for RDT (Rho = 0.80, p < 0.001) and microscopy (Rho = 0.75, p < 0.001) versus HRP2. RDT versus HRP2 positivity showed 24 states (64.9%) with overlapping 95% confidence intervals from the two independent surveys. P. falciparum prevalence estimates among 6-59-month-olds in Nigeria were highly concordant from two simultaneous, independently conducted household surveys, regardless of malaria test utilized. This provides evidence for the value of post-hoc laboratory HRP2 detection to leverage non-malaria surveys with similar sampling designs to obtain accurate P. falciparum estimates., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objectives: Determining an accurate estimate of SARS-CoV-2 seroprevalence has been challenging in African countries where malaria and other pathogens are endemic. We compared the performance of one single-antigen assay and three multi-antigen SARS-CoV-2 IgG assays in a Nigerian population endemic for malaria., Methods: De-identified plasma specimens from SARS-CoV-2 RT-PCR positive, dried blood spot (DBS) SARS-CoV-2 RT-PCR positive, and pre-pandemic negatives were used to evaluate the performance of the four SARS-CoV-2 assays (Tetracore, SARS2MBA, RightSign, xMAP)., Results: Results showed higher sensitivity with the multi-antigen (81% (Tetracore), 96% (SARS2MBA), 85% (xMAP)) versus the single-antigen (RightSign (64%)) SARS-CoV-2 assay. The overall specificities were 98% (Tetracore), 100% (SARS2MBA and RightSign), and 99% (xMAP). When stratified based on <15 days to ≥15 days post-RT-PCR confirmation, the sensitivities increased from 75% to 88.2% for Tetracore; from 93% to 100% for the SARS2MBA; from 58% to 73% for RightSign; and from 83% to 88% for xMAP. With DBS, there was no positive increase after 15-28 days for the three assays (Tetracore, SARS2MBA, and xMAP)., Conclusion: Multi-antigen assays performed well in Nigeria, even with samples with known malaria reactivity, and might provide more accurate measures of COVID-19 seroprevalence and vaccine efficacy., Competing Interests: The authors have no conflicts of interest to declare.

The US President's Emergency Plan for AIDS Relief (PEPFAR) supports molecular HIV and tuberculosis diagnostic networks and information management systems in low- and middle-income countries. We describe how national programs leveraged these PEPFAR-supported laboratory resources for SARS-CoV-2 testing during the COVID-19 pandemic. We sent a spreadsheet template consisting of 46 indicators for assessing the use of PEPFAR-supported diagnostic networks for COVID-19 pandemic response activities during April 1, 2020, to March 31, 2021, to 27 PEPFAR-supported countries or regions. A total of 109 PEPFAR-supported centralized HIV viral load and early infant diagnosis laboratories and 138 decentralized HIV and TB sites reported performing SARS-CoV-2 testing in 16 countries. Together, these sites contributed to >3.4 million SARS-CoV-2 tests during the 1-year period. Our findings illustrate that PEPFAR-supported diagnostic networks provided a wide range of resources to respond to emergency COVID-19 diagnostic testing in 16 low- and middle-income countries.

Human Immunodeficiency Virus (HIV) diagnosis remains the gateway to HIV care and treatment. However, due to changes in HIV prevalence and testing coverage across different geopolitical zones, it is crucial to evaluate the national HIV testing algorithm as false positivity due to low prevalence could be detrimental to both the client and the service delivery. Therefore, we evaluated the performance of the national HIV rapid testing algorithm using specimens collected from multiple HIV testing services (HTS) sites and compared the results from different HIV prevalence levels across the six geopolitical zones of Nigeria. The evaluation employed a dual approach, retrospective, and prospective. The retrospective evaluation focused on a desktop review of program data (n = 492,880) collated from patients attending routine HTS from six geopolitical zones of Nigeria between January 2017 and December 2019. The prospective component utilized samples (n = 2,895) collected from the field at the HTS and tested using the current national serial HIV rapid testing algorithm. These samples were transported to the National Reference Laboratory (NRL), Abuja, and were re-tested using the national HIV rapid testing algorithm and HIV-1/2 supplementary assays (Geenius to confirm positives and resolve discordance and multiplex assay). The retrospective component of the study revealed that the overall proportion of HIV positives, based on the selected areas, was 5.7% (28,319/492,880) within the study period, and the discordant rate between tests 1 and 2 was 1.1%. The prospective component of the study indicated no significant differences between the test performed at the field using the national HIV rapid testing algorithm and the re-testing performed at the NRL. The comparison between the test performed at the field using the national HIV rapid testing algorithm and Geenius HIV-1/2 supplementary assay showed an agreement rate of 95.2%, while that of the NRL was 99.3%. In addition, the comparison of the field results with HIV multiplex assay indicated a sensitivity of 96.6%, the specificity of 98.2%, PPV of 97.0%, and Kappa Statistic of 0.95, and that of the NRL with HIV multiplex assay was 99.2%, 99.4%, 99.0%, and 0.99, respectively. Results show that the Nigeria national serial HIV rapid testing algorithm performed very well across the target settings. However, the algorithm's performance in the field was lower than the performance outcomes under a controlled environment in the NRL. There is a need to target testers in the field for routine continuous quality improvement implementation, including refresher trainings as necessary., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: The introduction of human immunodeficiency virus (HIV) antibody rapid testing (RT) in resource-limited settings has proven to be a successful intervention to increase access to prevention measures and improve timely linkage to care. However, the quality of testing has not always kept pace with the scale-up of this testing strategy. To monitor the accuracy of HIV RT test results, a national proficiency testing (PT) program was rolled out at selected testing sites in Ghana using the dried tube specimen (DTS) approach., Methods: Between 2015 and 2018, 635 HIV testing sites, located in five regions and supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), were enrolled in the HIV PT program of the Ghana Health Service National AIDS/STI Control Programme. These sites offered various services: HIV Testing and Counselling (HTC), prevention of mother-to-child transmission (PMTCT) and Antiretroviral Treatment (ART). The PT panels, composed of six DTS, were prepared by two regional laboratories, using fully characterized plasma obtained from the regional blood banks and distributed to the testing sites. The results were scored by the PT providers according to the predefined acceptable performance criteria which was set at ≥ 95%., Results: Seven rounds of PT panels were completed successfully over three years. The number of sites enrolled increased from 205 in round 1 (June 2015) to 635 in round 7 (December 2018), with a noticeable increase in Greater Accra and Eastern regions. The average participation rates of enrolled sites ranged from 88.0% to 98.0% across the PT rounds. By round 7, HTC (257/635 (40.5%)) and PMTCT (237/635 (37.3%)) had a larger number of sites that participated in the PT program than laboratory (106/635 (16.7%)) and ART (12/635 (1.9%)) sites. The average testing performance rate improved significantly from 27% in round 1 to 80% in round 7 (p < 0.001). The highest performance rate was observed for ART (100%), HTC (92%), ANC/PMTCT (90%) and Laboratory (89%) in round 5., Conclusion: The DTS PT program showed a significant increase in the participation and performance rates during this period. Sub-optimal performances observed was attributed to non-compliance to the national testing algorithm and testing technique. However, the implementation of review meetings, peer-initiated corrective action, supportive supervisory training, and mentorship proved impactful. The decentralized approach to preparing the PT panels ensured ownership by the region and districts., Competing Interests: No competing interest identified by authors. This has been declared in the manuscript.

Background: The Nigeria AIDS Indicator and Impact Survey (NAIIS), a cross-sectional household survey, was conducted in 2018 with primary objectives to estimate HIV prevalence, HIV-1 incidence, and status of UNAIDS 90-90-90 cascade. We conducted retrospective analysis of the performance of HIV rapid tests and the national HIV testing algorithm used in Nigeria., Methods: The national algorithm included Determine HIV-1/2 as test 1 (T1), Unigold HIV-1/2 as test 2 (T2), and StatPak HIV-1/2 as the tie-breaker test (T3). Individuals reactive with T1 and either T2 or T3 were considered HIV-positive. HIV-positive specimens from the algorithm were further confirmed for the survey using supplemental test Geenius HIV-1/2. If Geenius did not confirm HIV-positive status, HIV-1 Western blot was performed. We calculated the concordance between tests and positive predictive value (PPV) of the algorithm on unweighted data., Results: Of 204,930 participants (ages ≥18 months) 5,103 (2.5%) were reactive on T1. Serial testing of T1 reactive specimens with T2 or if needed by tiebreaker T3 identified 2958 (1.44%) persons as HIV-positive. Supplemental testing confirmed 2,800 (95%) as HIV-positive (HIV-1 = 2,767 [98.8%]; HIV-2 = 5 [0.2%]; dual infections = 22 [0.8%]). Concordance between T1 and T2 was 56.6% while PPV of the national algorithm was 94.5%., Conclusions: Our results show high discordant rates and poor PPV of the national algorithm with a false-positive rate of about 5.5% in the NAIIS survey. Considering our findings have major implications for HIV diagnosis in routine HIV testing services, additional evaluation of testing algorithm is warranted in Nigeria., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Serosurveillance can provide estimates of population-level exposure to infectious pathogens and has been used extensively during the COVID-19 pandemic. Simultaneous, serological testing for multiple pathogens can be done using bead-based immunoassays to add value to disease-specific serosurveys. We conducted a validation of four SARS-CoV-2 antigens-full-length spike protein, two receptor binding domain proteins, and the nucleocapsid protein-on our existing multiplex bead assay (MBA) for enteric diseases, malaria, and vaccine preventable diseases. After determining the optimal conditions for coupling the antigens to microsphere beads, the sensitivity and specificity of the assay were determined on two instruments (Luminex-200 and MAGPIX) when testing singly (monoplex) versus combined (multiplex). Sensitivity was assessed using plasma from 87 real-time reverse transcription polymerase chain reaction (rRT-PCR) positive persons collected in March-May of 2020 and ranged from 94.3% to 96.6% for the different testing conditions. Specificity was assessed using 98 plasma specimens collected prior to December 2019 and plasma from 19 rRT-PCR negative persons and ranged from 97.4% to 100%. The positive percent agreement was 93.8% to 97.9% using 48 specimens collected > 21 days post-symptom onset, while the negative percent agreement was ≥ 99% for all antigens. Test performance was similar using monoplex or multiplex testing. Integrating SARS-CoV-2 serology with other diseases of public health interest could add significant value to public health programs that have suffered severe programmatic setbacks during the COVID-19 pandemic.

Objective: There is a need for reliable serological assays to determine accurate estimates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence. Most single target antigen assays have shown some limitations in Africa. To assess the performance of a multi-antigen assay, we evaluated a commercially available SARS-CoV-2 Multi-Antigen IgG assay for human coronavirus disease 2019 (COVID-19) in Nigeria., Methods: Validation of the xMAP SARS-CoV-2 Multi-Antigen IgG assay was carried out using well-characterized SARS-CoV-2 reverse transcription polymerase chain reactive positive (97) and pre-COVID-19 pandemic (86) plasma panels. Cross-reactivity was assessed using pre-COVID-19 pandemic plasma specimens (213) from the 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS)., Results: The overall sensitivity of the xMAP SARS-CoV-2 Multi-Antigen IgG assay was 75.3% [95% CI: 65.8%- 82.8%] and specificity was 99.0% [95% CI: 96.8%- 99.7%]. The sensitivity estimate increased to 83.3% [95% CI: 70.4%- 91.3%] for specimens >14 days post-confirmation of diagnosis. However, using the NAIIS pre-pandemic specimens, the false positivity rate was 1.4% (3/213)., Conclusions: Our results showed overall lower sensitivity and a comparable specificity with the manufacturer's validation. There appears to be less cross-reactivity with NAIIS pre-pandemic COVID-19 specimens using the xMAP SARS-CoV-2 Multi-Antigen IgG assay. In-country SARS-CoV-2 serology assay validation can help guide the best choice of assays in Africa., Competing Interests: The authors have declared that no competing interests exist.

Validated assays are essential for reliable serosurveys; however, most SARS-CoV-2 immunoassays have been validated using specimens from China, Europe, or U.S. populations. We evaluated the performance of five commercial SARS-CoV-2 immunoassays to inform their use in serosurveys in Nigeria. Four semiquantitative enzyme-linked immunosorbent assays (ELISAs) (Euroimmun anti-SARS-CoV-2 nucleocapsid protein [NCP] immunoglobulin G [IgG], Euroimmun spike SARS-CoV-2 IgG, Mologic Omega COVID-19 IgG, Bio-Rad Platelia SARS-CoV-2 Total Ab) and one chemiluminescent microparticle immunoassay (Abbott Architect SARS-CoV-2 IgG) were evaluated. We estimated the analytical performance characteristics using plasma from 100 SARS-CoV-2 PCR-positive patients from varied time points post-PCR confirmation and 100 prepandemic samples (50 HIV positive and 50 hepatitis B positive). The Bio-Rad assay failed the manufacturer-specified validation steps. The Euroimmun NCP, Euroimmun spike, and Mologic assays had sensitivities of 73.7%, 74.4%, and 76.9%, respectively, on samples taken 15 to 58 days after PCR confirmation and specificities of 97%, 100%, and 83.8%, respectively. The Abbott assay had 71.3% sensitivity and 100% specificity on the same panel. Parallel or serial algorithms combining two tests did not substantially improve the sensitivity or specificity. Our results showed lower sensitivity and, for one immunoassay, lower specificity compared to the manufacturers' results and other reported validations. Seroprevalence estimates using these assays might need to be interpreted with caution in Nigeria and similar settings. These findings highlight the importance of in-country validations of SARS-CoV-2 serological assays prior to use to ensure that accurate results are available for public health decision-making to control the COVID-19 pandemic in Africa. IMPORTANCE This study used positive and negative sample panels from Nigeria to test the performance of several commercially available SARS-CoV-2 serological assays. Using these prepandemic and SARS-CoV-2-positive samples, we found much lower levels of sensitivity in four commercially available assays than most assay manufacturer reports and independent evaluations. The use of these assays with suboptimal sensitivity and specificity in Nigeria or countries with population exposure to similar endemic pathogens could lead to a biased estimate of the seroprevalence, over- or underestimating the true disease prevalence, and limit efforts to stop the spread of SARS-CoV-2. It is important to conduct in-country validations of serological SARS-CoV-2 assays prior to their widespread use, especially in countries with limited representation in published assay validations.

Multiplex assays for malaria antigen detection can gather data from large sample sets, but considerations for the consistency and quality assurance (QA) of mass testing lack evaluation. We present a QA framework for a study occurring November 2019 to March 2020 involving 504 assay plates detecting four Plasmodium antigens: pan-Plasmodium aldolase and lactate dehydrogenase (LDH), histidine-rich protein 2 (HRP2), P. vivax LDH (PvLDH). Controls on each plate included buffer blank, antigen negative blood, and 4-point positive dilution curve. The blank and negative blood provided consistently low signal for all targets except for pAldolase, which showed variability. Positive curve signals decreased throughout the 5-month study duration but retained a coefficient of variation (CV) of < 5%, with the exception of HRP2 in month 5 (CV of 11%). Regression fittings for inter-plate control signals provided mean and standard deviations (SDs), and of 504 assay plates, 6 (1.2%) violated the acceptable deviation limits and were repeated. For the 40,272 human blood samples assayed in this study, of 161,088 potential data points (each sample × 4 antigens), 160,641 (99.7%) successfully passed quality checks. The QA framework presented here can be utilized to ensure quality of laboratory antigen detection for large sample sets.

Accurate SARS-CoV-2 serological assays are critical for COVID-19 serosurveillance. However, previous studies have indicated possible cross-reactivity of these assays, including in areas where malaria is endemic. We tested 213 well-characterized prepandemic samples from Nigeria using two SARS-CoV-2 serological assays, Abbott Architect IgG and Euroimmun NCP IgG assay, both targeting SARS-CoV-2 nucleocapsid protein. To assess antibody binding strength, an avidity assay was performed on these samples and on plasma from SARS-CoV-2 PCR-positive persons. Thirteen (6.1%) of 212 samples run on the Abbott assay and 38 (17.8%) of 213 run on the Euroimmun assay were positive. Anti- Plasmodium IgG levels were significantly higher among false positives for both Abbott and Euroimmun; no association was found with active Plasmodium falciparum infection. An avidity assay using various concentrations of urea wash in the Euroimmun assay reduced loosely bound IgG: of 37 positive/borderline prepandemic samples, 46%, 86%, 89%, and 97% became negative using 2 M, 4 M, 5 M, and 8 M urea washes, respectively. The wash slightly reduced avidity of antibodies from SARS-CoV-2 patients within 28 days of PCR confirmation; thereafter, avidity increased for all urea concentrations except 8 M. This validation found moderate to substantial cross-reactivity on two SARS-CoV-2 serological assays using samples from a setting where malaria is endemic. A simple urea wash appeared to alleviate issues of cross-reactivity.

The Mozambique Indicators of Immunization, Malaria and HIV/AIDS (IMASIDA) survey was conducted in 2015 and used a two Enzyme Immunoassay (EIA) (Vironostika HIV-1/2 and Murex HIV-1/2) based algorithm to determine the HIV status of the consented participants. The Mozambique Ministry of Health, with support from the US Centers for Disease Control and Prevention (US CDC), added Bio-Rad Geenius™ HIV-1/2 Supplemental Assay to the IMASIDA HIV testing algorithm to confirm all specimens that were found to be reactive on one or both EIAs. In total 11690 specimens were collected to estimate the proportion of HIV positive samples. Results indicate that the proportion of HIV positive samples based on the concordant positive results of two EIA assays was 21.5% (2518/11690). The addition of the Geenius assay to the IMASIDA HIV testing algorithm demonstrated that 792 (31.5%) of 2518 specimens were false-positive and reduced the proportion of HIV positive samples to 14.7% (1722/11690), demonstrating the importance of including a highly specific HIV test to confirm HIV diagnosis. HIV surveys exclusively based on EIA testing algorithm may result in misleading high prevalence results. Our results demonstrate that more specific confirmatory testing should be added to the EIA-based algorithms to ensure accurate HIV diagnosis and correct HIV prevalence estimate in cross-sectional surveys., Competing Interests: The authors have declared that no competing interests exist.

Overdiagnosis and overtreatment of malaria is a major problem in children in malaria-endemic countries. This retrospective study identified children who were admitted with fever and were treated with or without anti-malarial medications and discharged at the Paediatric Unit of the Effia-Nkwanta Regional Hospital. The medical records of all children were searched, retrieved and assessed. A total of 1160 records from children (age range, 0-12 years) were reviewed and evaluated. Of the total number, 21.3% had laboratory confirmed malaria, 38.4% were malaria negative, while 40.3% had no malaria tests performed. In addition, the results showed that 4.5% of the laboratory confirmed malaria positive cases were not given anti-malarial medication while 84.1% of the malaria negative cases were given these incorrectly. Furthermore, 78.2% of the children with no malaria tests were prescribed anti-malarial medication. The presumptive diagnosis of malaria should be abandoned and the installation of a functional laboratory services promoted., (© The Author(s) 2016.)

Background: An initial study of genetic diversity of Plasmodium falciparum in Asembo, western Kenya showed that the parasite maintained overall genetic stability 5 years after insecticide-treated bed net (ITN) introduction in 1997. This study investigates further the genetic diversity of P. falciparum 10 years after initial ITN introduction in the same study area and compares this with two other neighbouring areas, where ITNs were introduced in 1998 (Gem) and 2004 (Karemo)., Methods: From a cross-sectional survey conducted in 2007, 235 smear-positive blood samples collected from children ≤15-year-old in the original study area and two comparison areas were genotyped employing eight neutral microsatellites. Differences in multiple infections, allele frequency, parasite genetic diversity and parasite population structure between the three areas were assessed. Further, molecular data reported previously (1996 and 2001) were compared to the 2007 results in the original study area Asembo., Results: Overall proportion of multiple infections (MA) declined with time in the original study area Asembo (from 95.9 %-2001 to 87.7 %-2007). In the neighbouring areas, MA was lower in the site where ITNs were introduced in 1998 (Gem 83.7 %) compared to where they were introduced in 2004 (Karemo 96.7 %) in 2007. Overall mean allele count (MAC ~ 2.65) and overall unbiased heterozygosity (H e  ~ 0.77) remained unchanged in 1996, 2001 and 2007 in Asembo and was the same level across the two neighbouring areas in 2007. Overall parasite population differentiation remained low over time and in the three areas at FST < 0.04. Both pairwise and multilocus linkage disequilibrium showed limited to no significant association between alleles in Asembo (1996, 2001 and 2007) and between three areas., Conclusions: This study showed the P. falciparum high genetic diversity and parasite population resilience on samples collected 10 years apart and in different areas in western Kenya. The results highlight the need for long-term molecular monitoring after implementation and use of combined and intensive prevention and intervention measures in the region.

Background: Intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) has been adopted as policy by most countries in sub-Saharan Africa. This cross-sectional study assessed the prevalence of IPTp-SP usage for prevention of malaria among pregnant women as well as evaluated factors associated with IPTp-SP use during pregnancy in Sekondi-Takoradi region of Ghana., Methods: Pregnant women attending their antenatal-care with either clinical/ultrasound evidence of pregnancy were recruited. Venous blood was screened for malaria using RAPID response antibody kit and Giemsa staining. Haemoglobin estimations were done by cyanmethemoglobin method while Human Immunodeficiency Virus (HIV) screening was performed by the national diagnostic algorithm of two rapid antibody test and western blot confirmation., Results: Of the 754 consented pregnant women interviewed in this study, 57.8% had received IPTp-SP while 42.2% had not at their first contact with the study personnel. Furthermore, 18.6% (81/436) of those that received IPTp-SP were malaria positive while 81.4% (355/436) were malaria negative. The results also indicated that 47.7% (51/107) of the pregnant women in their third trimester who were meant to have received at least two-doses of SP had received ≥2 doses while 35.5% (38/107) had received 1 dose. In multivariable logistic regression analysis, pregnant women in their third trimester who received ≥2 doses of SP showed decreased likelihoods of malaria (adjusted OR, 0.042; 95% CI, 0.003-0.51; P = 0.013)., Conclusion: IPTp-SP usage among pregnant women in Sekondi-Takoradi reduces malaria and its use for malaria prevention should be strengthened with proper dosage completion and coverage.

Introduction: Children under five years of age are highly vulnerable to malaria infection and often face dire consequences such as severe malaria if they are not promptly and adequately treated with effective anti-malarial medications. We set out to evaluate malaria and associated co-morbidity among children admitted with febrile illness in Sekondi-Takoradi, Ghana., Methodology: This retrospective study focused on children admitted with fever over a three-year period at the pediatric unit of Effia-Nkwanta Regional Hospital. The children were identified, and the medical records of those who were successfully treated and discharged were searched, retrieved, and reviewed., Results: A total of 1,193 children were identified and selected for analysis. The mean duration of admission increased from 2.17 days in 2010 to 3.36 in 2012. Conversely, the mean age decreased from 3.85 years in 2010 to 2.74 in 2012. Overall, laboratory-confirmed malaria prevalence decreased; however, this decrease was only observed among children five years of age or younger, while malaria prevalence increased among children one year of age or younger. The proportion of children with severe malarial anemia significantly increased, while the proportion of those with mild malaria decreased significantly., Conclusions: Despite the general decrease in malaria morbidity seen in this study, children younger than one year of age remain at increased risk of malaria morbidity. With an increase in malaria prevalence among children younger than one year of age over the three years of study, integrated and targeted control measures are highly needed for this age group.

African American adolescent males who have sex with males (MSMs) have a high prevalence of sexually transmitted diseases (STDs) that has been directly linked to lack of access to primary care providers and reluctance to disclose their sexuality. The human papillomavirus (HPV) is the most common STD with more than 40 different serotypes and can lead to anal/genital warts as well as oral and genital cancers. The HPV vaccine if taken prior to an adolescent becoming sexually active serves a prophylactic function. The HPV vaccine is approved by the Food and Drug Administration (FDA) for girls and boys; however, HPV vaccination rates among adolescents within different minority and underserved communities have been disappointing even though these groups are disproportionately infected with the HPV virus and certain male-specific cancers. Little is known about the uptake of the vaccine among African American MSMs and thus the aim of this study. This qualitative study is based on the health belief model and assessed participants' level of awareness of HPV, the HPV vaccine, and HPV-related illnesses among 24 African American male adolescents between 16 and 18 years old who self identify as MSMs. As part of a larger study, two focus groups were conducted for African American MSMs. Participants failed to understand their potential risk for HPV given the higher rates of STD infection experienced by MSMs. They expressed very little knowledge of the HPV vaccine and are also not aware of the complications of HPV virus infection. However, they were very eager to know more about the virus and the vaccine. This study demonstrates the need for the development of health communication intervention and more research targeting African American MSMs and also the need for policy change towards making the HPV vaccine routine for males especially adolescents at no cost.

Background: The effectiveness of sulphadoxine-pyrimethamine (SP) intermittent preventive treatment of malaria in pregnancy (IPTp) might be compromised by high prevalence of resistance-associated Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutations. As a proxy for IPTp-SP effectiveness, the in vivo efficacy of SP to clear parasitaemia and prevent reinfection in asymptomatic parasitaemic pregnant women in an area with high SP resistance prevalence was assessed., Methods: Pregnant women 16-26 weeks' gestation with asymptomatic parasitaemia presenting for antenatal care were given IPTp-SP and followed for 42 days. The primary outcome was polymerase chain reaction (PCR) uncorrected 42-day survival rate; the per cent of patients without recrudescence or reinfection by day 42. PCR was used to distinguish recrudescence from reinfection. DNA was sequenced to detect resistance-associated dhfr and dhps mutations., Results: Of 245 pregnant women included in the intention-to-treat analysis, 93.9% cleared their parasitaemia by day 7. The day 42 PCR-uncorrected survival rate was 58.1% (95% confidence interval (CI) 51.5-65.7) and day 42 PCR-corrected survival was 68.7% (CI 61.4-76.0). Recrudescence was more common among primi- than among multigravid women; recrudescence rate 33.3% (CI 25.1-42.4%) versus 21.4% (CI 15.0-29.0%) (log rank test p-value 0.006). The quintuple mutant was present in nearly all samples (95%), while 2% were sextuple mutants with an additional mutation at dhps A581G., Conclusions: SP efficacy for acute malaria treatment has been compromised by resistance, but SP retains partial activity among pregnant women with asymptomatic parasitaemia, and thus might be useful for IPTp. Nonetheless, research on non-SP IPTp regimens should continue., Trial Registration: ClinicalTrials.gov NCT01120145 .

This study investigated the influence of the level of education on HIV infection among pregnant women attending antenatal care in Sekondi-Takoradi, Ghana. A cross-sectional study was conducted at four hospitals in the Sekondi-Takoradi metropolis. The study group comprised 885 consenting pregnant women attending antenatal care clinics. Questionnaires were administered and venous blood samples were screened for HIV and other parameters. Multivariable logistic regression analyses were performed to determine the association between the level of education attained by the pregnant women and their HIV statuses. The data showed that 9.83% (87/885) of the pregnant women were HIV seropositive while 90.17% (798/885) were HIV seronegative. There were significant differences in mean age (years) between the HIV seropositive women (27.45 ± 5.5) and their HIV seronegative (26.02 ± 5.6) counterparts (p = .026) but the inference disappeared after adjustment (p = .22). Multivariable logistic regression analysis revealed that pregnant women with secondary/tertiary education were less likely to have HIV infection compared with those with none/primary education (adjusted OR, 0.53; 95% CI, 0.30-0.91; p = .022). Our data showed an association with higher level of education and HIV statuses of the pregnant women. It is imperative to encourage formal education among pregnant women in this region.

Despite the recent advances in drug research, finding a safe, effective, and easy to use chemotherapy for human African trypanosomiasis (HAT) remains a challenging task. The four current anti-trypanosomiasis drugs have major disadvantages that limit more widespread use of these drugs in the endemic regions of sub-Saharan Africa. Pentamidine and suramin are limited by their effectiveness against the only first stage of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, respectively. In addition, melarsoprol and eflornithine (two second stage drugs) each have disadvantages of their own. The former is toxic and has increasing treatment failures while the latter is expensive, laborious to administer, and lacks efficacy against T. b. rhodesiense. Furthermore, melarsoprol's toxicity and decreasing efficacy are glaring problems and phasing out the drug as a frontline treatment against T. b. gambiense is now possible with the emergence of competent, safe combination chemotherapies such as nifurtimox-eflornithine combination treatment (NECT). The future of eflornithine, on the other hand, is more promising. The drug is useful in the context of combination chemotherapy and potential orally administered analogues. Due to the limits of monotherapies, greater emphasis should be placed on the research and development of combination chemotherapies, based on the successful clinical tests with NECT and its current use as a frontline anti-trypanosomiasis treatment. This review discussed the current and future chemotherapy strategies for the treatment of HAT.

Objective: To assess the burden of maternal malaria and HIV among pregnant women in Ghana and to determine the risk of anemia among women with dual infection., Methods: A cross-sectional study was conducted at 4 hospitals in the Sekondi-Takoradi metropolis, Ghana. The study group comprised 872 consenting pregnant women attending prenatal care clinics. Venous blood samples were screened for malaria, HIV, and hemoglobin level. Multivariate logistic regression analysis was performed to determine the association between malaria, HIV, and risk of anemia., Results: In all, 34.4% of the study cohort had anemia. Multivariate logistic regression analysis indicated that pregnant women with either malaria (odds ratio 1.99; 95% confidence interval, 1.43-2.77; P=<0.001) or HIV (odds ratio 1.78; 95% confidence interval, 1.13-2.80; P=0.014) had an increased risk of anemia. In adjusted models, pregnant women co-infected with both malaria and HIV displayed twice the risk of anemia. The adjusted odds ratio was 2.67 (95% confidence interval, 1.44-4.97; P=0.002)., Conclusion: Pregnant women infected with both malaria and HIV are twice as likely to be anemic than women with a single infection or no infection. Measures to control malaria, HIV, and anemia during pregnancy are imperative to improve birth outcomes in this region of Ghana., (Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Immunoglobulin (Ig) GM and KM allotypes, genetic markers of γ and κ chains, are associated with humoral immune responsiveness. Previous studies have shown the relationships between GM6-carrying haplotypes and susceptibility to malaria infection in children and adults; however, the role of the genetic markers in placental malaria (PM) infection and PM with HIV co-infection during pregnancy has not been investigated. We examined the relationship between the gene polymorphisms of Ig GM6 and KM allotypes and the risk of PM infection in pregnant women with known HIV status. DNA samples from 728 pregnant women were genotyped for GM6 and KM alleles using polymerase chain reaction-restriction fragment length polymorphism method. Individual GM6 and KM genotypes and the combined GM6 and KM genotypes were assessed in relation to PM in HIV-1 negative and positive women, respectively. There was no significant effect of individual GM6 and KM genotypes on the risk of PM infection in HIV-1 negative and positive women. However, the combination of homozygosity for GM6(+) and KM3 was associated with decreased risk of PM (adjusted OR, 0.25; 95% CI, 0.08-0.8; P = 0.019) in HIV-1 negative women while in HIV-1 positive women the combination of GM6(+/-) with either KM1-3 or KM1 was associated with increased risk of PM infection (adjusted OR, 2.10; 95% CI, 1.18-3.73; P = 0.011). Hardy-Weinberg Equilibrium (HWE) tests further showed an overall significant positive F(is) (indication of deficit in heterozygotes) for GM6 while there was no deviation for KM genotype frequency from HWE in the same population. These findings suggest that the combination of homozygous GM6(+) and KM3 may protect against PM in HIV-1 negative women while the HIV-1 positive women with heterozygous GM6(+/-) combined with KM1-3 or KM1 may be more susceptible to PM infection. The deficit in heterozygotes for GM6 further suggests that GM6 could be under selection likely by malaria infection.

A malaria vaccine targeting Plasmodium falciparum remains a strategic goal for malaria control. If a polyvalent vaccine is to be developed, its subunits would probably be chosen based on immunogenicity (concentration of elicited antibodies) and associations of selected antigens with protection. We propose an additional possible selection criterion for the inclusion of subunit antigens; that is, coordination between elicited antibodies. For the quantitative estimation of this coordination, we developed a malaria serological map (MSM). Construction of the MSM was based on three categories of variables: (i) malaria antigens, (ii) total IgG and IgG subclasses, (iii) different sources of plasma. To validate the MSM, in this study, we used four malaria antigens (AMA1, MSP2-3D7, MSP2-FC27 and Pf332-C231) and re-grouped the plasma samples into five pairs of subsets based on age, gender, residence, HbAS and malaria morbidity in 9 years. The plasma total IgG and IgG subclasses to the test antigens were measured, and the whole material was used for the MSM construction. Most of the variables in the MSM were previously tested and their associations with malaria morbidity are known. The coordination of response to each antigens pair in the MSM was quantified as the correlation rate (CR = overall number of significant correlations/total number of correlations × 100 %). Unexpectedly, the results showed that low CRs were mostly associated with variables linked with malaria protection and the antigen eliciting the least CRs was the one associated with protection. The MSM is, thus, of potential value for vaccine design and understanding of malaria natural immunity.

The problem of malaria in adolescence has been surpassed by the immense burden of malaria in children, most especially less than 5. A substantial amount of work done on malaria in pregnancy in endemic regions has not properly considered the adolescence. The present study therefore aimed at evaluating the prevalence of Plasmodium falciparum and anaemia infection in adolescent pregnant girls in the Sekondi-Takoradi metropolis, Ghana. The study was carried out at four hospitals in the Sekondi-Takoradi metropolis of the western region of Ghana from January 2010 to October 2010. Structured questionnaires were administered to the consenting pregnant women during their antenatal care visits. Information on education, age, gravidae, occupation and socio-demographic characteristics were recorded. Venous bloods were screened for malaria using RAPID response antibody kit and Geimsa staining while haemoglobin estimations were done by cyanmethemoglobin method. The results revealed that adolescent pregnant girls were more likely to have malaria infection than the adult pregnant women (34.6% verses 21.3%, adjusted OR 1.65, 95% CI, 1.03-2.65, P=0.039). In addition, adolescent pregnant girls had higher odds of anaemia than their adult pregnant women equivalent (43.9% versus 33.2%; adjusted OR 1.63, 95% CI, 1.01-2.62, P=0.046). Taken together, these data suggest that adolescent pregnant girls were more likely to have malaria and anaemia compared to their adult pregnant counterpart. Results from this study shows that proactive adolescent friendly policies and control programmes for malaria and anaemia are needed in this region in order to protect this vulnerable group of pregnant women., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Resistance to sulphadoxine-pyrimethamine (SP) in Plasmodium falciparum parasites is associated with mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes and has spread worldwide. SP remains the recommended drug for intermittent preventive treatment for malaria in pregnancy (IPTp) and information on population prevalence of the SP resistance molecular markers in pregnant women is limited., Methods: Temporal trends of SP resistance molecular markers were investigated in 489 parasite samples collected from pregnant women at delivery from three different observational studies between 1996 and 2009 in Kenya, where SP was adopted for both IPTp and case treatment policies in 1998. Using real-time polymerase chain reaction, pyrosequencing and direct sequencing, 10 single-nucleotide polymorphisms (SNPs) of SP resistance molecular markers were assayed., Results: The prevalence of quintuple mutant (dhfr N51I/C59R/S108N and dhps A437G/K540E combined genotype) increased from 7% in the first study (1996-2000) to 88% in the third study (2008-2009). When further stratified by sample collection year and adoption of IPTp policy, the prevalence of the quintuple mutant increased from 2.4% in 1998 to 44.4% three years after IPTp policy adoption, seemingly in parallel with the increase in percentage of SP use in pregnancy. However, in the 1996-2000 study, more mutations in the combined dhfr/dhps genotype were associated with SP use during pregnancy only in univariable analysis and no associations were detected in the 2002-2008 and 2008-2009 studies. In addition, in the 2008-2009 study, 5.3% of the parasite samples carried the dhps triple mutant (A437G/K540E/A581G). There were no differences in the prevalence of SP mutant genotypes between the parasite samples from HIV + and HIV- women over time and between paired peripheral and placental samples., Conclusions: There was a significant increase in dhfr/dhps quintuple mutant and the emergence of new genotype containing dhps 581 in the parasites from pregnant women in western Kenya over 13 years. IPTp adoption and SP use in pregnancy only played a minor role in the increased drug-resistant parasites in the pregnant women over time. Most likely, other major factors, such as the high prevalence of resistant parasites selected by the use of SP for case management in large non-pregnant population, might have contributed to the temporally increased prevalence of SP resistant parasites in pregnant women. Further investigations are needed to determine the linkage between SP drug resistance markers and efficacy of IPTp-SP.

Malaria signature on human genome is marked by several gene polymorphisms. HemoglobinAS (HbAS) is known to protect against severe malaria, but barely proved to protect against uncomplicated malaria (UM). Similarly, the influence of FcγRIIa-RH131 polymorphism on malaria is controversial. Polymorphisms in both genes were examined and levels of IgG subclasses against four malaria antigens were measured for 250 Fulani's from Daraweesh, eastern Sudan. Morbidity data for up to nine years was available for 214 donors. Number of malaria episodes experienced by each individual during the study period was used as indicator for susceptibility to UM. PCR and RFLP were used for donors DNA genotyping and ELISA for antibodies measurement. Results revealed that neither FcγRIIa-RH131 alleles/genotypes nor HbAA/AS was significantly associated with malaria morbidity or with levels of IgG to test antigens. Both polymorphisms were in Hardy-Weinberg Equilibrium, interestingly, there was strong association between the two polymorphisms (linkage disequilibrium - LD) with D' = 0.89. The association between the two polymorphisms was confirmed by analysis of independent material from a neighboring village. In conclusion, in Daraweesh both FcγRIIa-RH131 and HbAA/AS genotypes, independently or together, were not major markers for UM susceptibility, however, marked LD was observed between the two polymorphisms., (Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Background: Intestinal parasites are endemic in many parts of the world where HIV infection is also widespread. Previous studies had shown that the spectrum of opportunistic and common endemic parasitic infections with HIV vary in different regions and usually reflect the infections prevalent in these regions. This present study was aimed at comparing the prevalence and types of intestinal parasitic infections in HIV sero-positive and sero-negative patients in Lagos., Materials and Methods: Venous blood and stool samples of 1080 patients, recruited from three health care institutions were screened for HIV infection and intestinal parasites using HIV-1, HIV-2 rapid tests, direct wet mount with saline/iodine and formol-ether technique, respectively., Results: Results showed that 6% (65/1080) of patients were sero-positive for HIV infection. In addition, 23.3% (252/1080) patients were infected with intestinal parasites and 33.8% (22/65) of patients with HIV had intestinal parasites co-infections. The prevalence of Entamoeba histolytica/Entamoeba dispar, Entamoeba coli, Iodamoeba butschilii, Giardia intestinalis, and Hookworm were statistically significantly higher among HIV sero-positive patients as compared to the HIV sero-negative patients. In addition, HIV sero-positive patients had higher odds of mixed intestinal parasites than the HIV sero-negative patients (9.1% versus 3.9%; adjusted OR 2.05, 95% CI, 1.14-3.72, P=0.021)., Conclusion: In this study population, HIV sero-positive patients were more likely to have intestinal parasitic infections. The study underscores the public health significance of intestinal parasitic infections in HIV infected individuals., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The anti-malarial IgG immune response during the lengthy and dry season in areas of low malaria transmission as in Eastern Sudan is largely unknown. In this study, ELISA was used for the measurement of pre-existing total IgG and IgG subclasses to a panel of malaria antigens, MSP2-3D7, MSP2-FC27, AMA-1 and Pf332-C231. The results showed that the antibody responses were predominantly age dependent, antigen specific, and their lifespan was at least 5-6 month long. Generally, the IgG3 was most abundant IgG subclass, and the most recognized antigen was Pf332-C231. Furthermore, the correlation between the levels of IgG subclasses was strongest between IgG1 and IgG3, which were more predictive to the total IgG levels. Finally, the response pattern of each of the IgG subclasses to the different test antigens that were spanning the dry season and the correlation between these responses were described in details for the first time., (© 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.)

Susceptibility to uncomplicated malaria (UM), as to other forms of the disease, is genetically determined. Over 9-years of clinical and parasitological follow up of inhabitants of Daraweesh, in Eastern Sudan, the relative susceptibility to UM was estimated in terms of number of episodes experienced by each individual. Previously, we reported that the levels of IgG2 and IgG3 to Pf332-C231 malaria antigen are negatively correlated with number of malaria episodes. In addition, four molecular markers for malaria susceptibility (CRP -286, GM/KM haplotypes, FcγRIIa131 and HbAS) were tested. In this study, the above data were combined and reanalysed. The CRP -286A allele and GM 1,17 5,13,14,6 phenotype were previously found to be associated with increased susceptibility to malaria; however, individuals have both polymorphism together were not more susceptible to UM than the non-carriers of the same double polymorphism. The FcγRIIa-RR131 and HbAA genotypes taken individually or as double polymorphism were not associated with malaria susceptibility; however, their combination with any or both of the former polymorphisms was mostly associated with increased susceptibility to malaria. None of the four markers were associated with the levels of IgG2 and IgG3 against Pf332-C231. In conclusion, while our data support the polygenic nature of susceptibility to UM and highlighted the role of immune markers polymorphisms, the combinations of these markers were not predictable, i.e. the combination of the susceptibility markers will not necessarily render the carriers more susceptible to UM., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background & Objectives: Little information exists on the compliance of pregnant women to malaria management in malaria endemic countries. This study was designed to access knowledge, attitude, perception and home management of malaria among consenting pregnant women attending antenatal care (ANC) clinic., Methods: In total, 350 pregnant women were randomly recruited during their ANC Clinic in Lagos. Structured questionnaires were administered in a two-stages research design; first during their early months of ANC visit and the second approximately 1-2 months before delivery. Information on occupation, parity, symptoms used to recognise malaria, treatment sources, control measures, knowledge factors, anti-vector measures, health-seeking practices, malaria parasitaemia and packed cell volume (PCV) were recorded., Results: The results revealed that 78.9% of the pregnant women identified infected mosquitoes as the cause of malaria while 86% of the pregnant women identified stagnant water as its breeding sites. Knowledge of the benefit of insecticide-treated mosquito bednets was less prominent as most of the selected subjects decried its high market price. Our data also showed that educational programme targeted on potential mothers is beneficial. Overall, 27.4% (96/350) of the pregnant women had peripheral malaria infection with 88.5% (85/96) of the parasite positive women infected with Plasmodium falciparum and 11.5% (11/96) with P. malariae. PCV ranged from 20-40% (median 33.9%) with 25.7% (90/350) of the pregnant women being anaemic with PCV <33%. We found an association between malaria infection and occupation, and this association was not influenced by parity., Interpretation & Conclusion: Our findings revealed that improvement in knowledge and education of women of child-bearing age has an influential impact on malaria control.

In malaria, drug resistance and treatment failure (TF) are not synonymous, although are escalating together. Over 9 years of surveillances for malaria morbidity and TF in Daraweesh village in eastern Sudan (1991-2004), 136 donors (15-78 years) from 43 households, treated for 278 malaria episodes and had experienced 46 incident of TF, were included in this study. Blood obtained from the donors in 2005, was used for measurement of IgG subclasses against Pf332-C231 antigen and GM/KM allotyping and for genotyping of the donors for; FcgammaRIIA 131 (HH, RH, RR), CRP 286 (C

The immune system is a highly evolved network of cells and molecules that can distinguish between invading pathogens and the body's own cells. But helminths, in their complex forms, are capable of down-regulating host immunity, protecting them from being eliminated and also minimizing severe pathology in the host. This review focuses on Strongyloides stercoralis and the immune responses in immunocompetent and/or immunocompromised individuals. It also highlights the implications for diagnosis/treatment and draws attention to an emerging public health disease. The solution to reducing the prevalence of strongyloidiasis remains on the effectiveness of pre-emptive measures in endemic communities, increased awareness, prompt early diagnosis as well as timely treatment., (Crown Copyright 2009. Published by Elsevier Ireland Ltd. All rights reserved.)

The certainty of the protective role of acquired immunity in malaria is the major drive for malaria vaccine development. In this study, we measured the levels of total IgG and IgG subclasses to four candidate malaria vaccine antigens; MSP2-3D7, MSP2-FC27, AMA-1 and Pf332-C231, in plasma obtained from a cohort of 136 donors from Daraweesh in Sudan. The cohort was followed for malaria infection for 9 years. After an initial analysis, the immune response to Pf332-C231 antigen was the only one found associated with protection, thus taken for further analysis. The number of previous clinical malaria episodes experienced by the donors was used as an index for relative protection. The number of these episodes was found to be negatively correlated with the levels of pre-existing total IgG, IgG2 and IgG3 to Pf332-C231 (correlation coefficient, CC - 0.215, p=0.012; CC - 0.195, p=0.023 and CC - 0.211, p=0.014, respectively), and also with age (CC - 0.311, p<0.001). Unexpectedly, equal levels of Pf332-C231 antibodies were induced by both patent and sub-patent infections regardless of the number of previous malaria episodes (1-7). Combining the correlation analysis with a multi-linear regression, three variable markers for protection were emerged, two age-dependent, the antibody response to Pf332-C231 and an unidentified marker (likely immune response to other antigens), and the third was an age-independent unidentified marker (possibly gene polymorphisms). In conclusion, this report suggests a protective effect for IgG subclasses to Pf332-C231 antigen against malaria., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Background: Plasmodium falciparum malaria is a complex disease in which genetic and environmental factors influence susceptibility. IgG isotypes are in part genetically controlled, and GM/KM allotypes are believed to be involved in this control., Methods: In this study, 216 individuals from Daraweesh, an area of seasonal malaria transmission in Sudan, were followed for nine years for malaria infection. Total IgG and IgG isotypes against four malaria antigens, MSP2-3D7, MSP2-FC27, AMA1, and Pf332-C231 were measured in plasma obtained from the cohort at the end of the study, during the dry malaria-free period. The GM/KM allotypes of the donors were determined., Results: The GM 1,17 5,13,14,6 phenotype was associated with a higher incidence of malaria compared with the non-1,17 5,13,14,6 phenotypes (P = 0.037). Paradoxically, the carriers of the GM 1,17 5,13,14,6 phenotype had significantly higher baseline levels of total IgG and non-cytophilic IgG isotypes as compared to non-carriers. The KM allotypes influence on IgG isotypes level was limited. Finally, the differences in the baseline concentrations of total IgG and IgG isotypes between the different GK/KM phenotype carriers were antigen-dependent., Discussion: The results show that GM but not KM allotypes appeared to influence host susceptibility to uncomplicated malaria as well as the antibody profile of the donors, and the carriers of the GM 1,17 5,13,14,6 phenotype were the most susceptible, Conclusions: The GM allotypes have significant influence on susceptibility to uncomplicated P. falciparum malaria and antigen-dependent influence on total IgG and IgG subclasses.

Background: The ability of the host immune system to efficiently clear Plasmodium falciparum parasites during a malaria infection depends on the type of immune response mounted by the host., Study Design: In a cross-sectional study, we investigated the cellular-and antibody responses in individuals with P. falciparum infection, in an attempt to identify immunological signs indicative of the development of natural immunity against malaria in Ibadan, Nigeria. Levels of IL-10, IL-12(p70), IFN-gamma, and IgM, IgG and IgG1-4 subclasses in the serum of 36 symptomatic children with microscopically confirmed malaria parasitaemia and 54 asymptomatic controls were analysed by ELISA., Results: IFN-gamma and IL-10 were significantly higher in the symptomatic children (p=0.009, p=0.025 respectively) than in the asymptomatic controls but no differences were seen for IL-12(p70). Estimated higher ratios of IFN-gamma/IL-10 and IFN-gamma/IL-12 were also observed in the symptomatic children while the asymptomatic controls had higher IL-12/IL-10 ratio. The mean concentration levels of anti-P. falciparum IgG1, IgG2, IgG3 antibodies were statistically significantly higher in the individuals >5 years of age than <5 years while anti-P. falciparum IgG3 antibodies were notably low in <5 years category. Children <5 years had higher IgM antibodies than IgG and the expression of IgG subclasses increased with age., Conclusion: Taken together, malaria infection is on a delicate balance of pro- and anti-inflammatory cytokines. The higher levels of IFN-gamma seen in the symptomatic children (<6 months) may be instrumental in immune-protection against malaria by limiting parasite replication. The observed variations in immunoglobulin subclass levels were age-dependent and exposure-related.

Background: A SNP at position 131, in the FcgammaRIIa gene, affects the binding of the different IgG subclasses and may influence the clinical variation seen in patients with falciparum malaria. This study confirms and extends previous findings, analysing the FcgammaRIIa (CD32) polymorphism in relation to the IgG subclass distribution seen among two sympatric tribes living in eastern Sudan, characterized by marked differences in susceptibility to Plasmodium falciparum malaria., Methods: Two hundred and fifty Fulani subjects living in an area of meso-endemic P. falciparum malaria infection were genotyped for the FcgammaRIIa-131 polymorphism. For comparison, 101 non-Fulani donors - (Masaleit, Hausa and Four) - living in the same study area, were genotyped. The levels of plasma antibodies (IgG and subclasses) to four malaria antigens (AMA-1, MSP 2 - 3D7 & FC27, Pf332-C231) were measured using indirect enzyme-linked immunosorbent assays., Results: The FcgammaRIIa-H/H131 genotype was found to be significantly more prevalent in the Fulani as compared to the non-Fulani ethnic groups (36.0% for Fulani versus 17.8% for non-Fulani, adjusted OR 3.10, 95% CI 1.61-5.97, P value < 0.001). The Fulani showed lower anti-malarial IgG1 and IgG3 antibody levels as compared to the non-Fulani and higher levels of IgG2 antibodies., Conclusion: The FcgammaRIIa-H/H131 genotype and H131 allele is at higher frequency in the Fulani ethnic group. The H/H131 genotype was consistently associated with higher levels of anti-malarial IgG2 and IgG3 antibodies, while the R/R131 genotype was associated with higher levels of IgG1 antibodies.

Despite many intervention programmes aimed at curtailing the scourge, malaria remains a formidable problem of human health. Immunity to asexual blood-stage of Plasmodium falciparum malaria is thought to be associated with protective antibodies of certain immunoglobulin classes and subclasses. We have analysed immunoglobulin G profiles to six leading blood-stage antigens in relation to clinical malaria outcome in a hospital-based study in Sudan. Our results revealed a linear association with anti-AMA-1-IgG1 antibodies in children <5 years and reduced risk of severe malaria, while the responses of the IgG3 antibodies against MSP-2, MSP-3, GLURP in individuals above 5 years were bi-modal. A dominance of IgG3 antibodies in >5 years was also observed. In the final combined model, the highest levels of IgG1 antibodies to AMA-1, GLURP-R0, and the highest levels of IgG3 antibodies to 3D7 MSP-2 were independently associated with protection from clinical malaria. The study provides further support for the potential importance of the studied merozoite vaccine candidate antigens as targets for parasite neutralizing antibody responses of the IgG1 and IgG3 subclasses.

Background: The Ig Fc receptor family is an important link between the humoral and cellular immune systems. The association of a dimorphism in amino acid 131 (R/H) of the FcgammaRIIa with malaria severity, the R-allele being associated with a milder disease outcome, led to the investigation of the possible impact of this polymorphism in the interethnic difference in malaria susceptibility seen between the Fulani and Dogon in Mali., Methods: Plasma from individuals from Mali (164 Fulani and 164 Dogon) were analysed for malaria-reactive and total IgG subclass antibodies using ELISA, and the same individuals were also genotyped for the FcgammaRIIa R131H polymorphism using RFLP-PCR. Statistical analyses of the IgG subclass levels were done by unpaired t-test and ANOVA, and genotype differences were tested by chi2-test., Results: While the two ethnic groups showed a similar frequency of the FcgammaRIIa 131 R/H heterozygote genotype, 131R/R dominated over the 131 H/H genotype in the Dogon whereas the Fulani presented a similar frequency of the two homozygote genotypes. The two alleles were evenly distributed in the Fulani, while the Dogon were clearly biased towards the R-allele. The Fulani showed higher levels of anti-malarial IgG1, -2 and -3 antibodies, with a higher proportion of IgG2, than the Dogon. In the Fulani, H-allele carriers had higher anti-malarial IgG2 levels than R/R homozygotes, while in the Dogon, the R-allele carriers showed the higher IgG2 levels. For anti-malarial IgG3, the R-allele carriers in the Fulani had higher levels than the H/H homozygotes., Conclusion: Taken together, the results showed marked interethnic differences in FcgammaRIIa R131H genotypes. Furthermore, the results indicate that the FcgammaRIIa R131H genotype may influence the IgG subclass responses related to protection against malaria, and that IgG2 may be of importance in this context.

Dracunculiasis is a preventable parasitic disease that for many years has affected poor communities without a safe portable water supply. Transmission is basically limited among the nomadic in remote rural settings. Most countries, including Asia, are declared free from the Guinea worm disease restraining the burden of transmission to Africa especially Sudan, Ghana, Mali, Nigeria and Niger. This review focuses mainly on the progress made so far by the Global Guinea Worm Eradication Programme championed by the Carter Center, Centers for Disease Control and Prevention, World Health Organisation, The United Nations Children's Fund and the individual efforts of endemic nations through their National Guinea Worm Eradication Programme aimed towards total global Guinea worm eradication.

In a prospective clinical study in New Halfa Teaching Hospital, the possible association between FcgammaRIIa-R/H131 polymorphism and anti-malarial antibody responses with clinical outcome of Plasmodium falciparum malaria among Sudanese patients was investigated. A total of 256 individuals were consecutively enrolled, comprising 115 patients with severe malaria, 85 with mild malaria and 56 malaria-free controls. Genotyping of FcgammaRIIa-R/H131 dimorphism was performed using gene-specific polymerase chain reaction (PCR) amplification with allele-specific restriction enzyme digestion of the PCR product. The antibody responses to asexual blood-stage antigens were assessed by an enzyme-linked immunosorbent assay. The frequency of the FcgammaRIIa-R/R131 genotype was significantly higher in those with severe malaria when compared with patients with mild malaria, while the FcgammaRIIa-H/H131 genotype showed a significant association with mild malaria. A reduced risk of severe malaria with IgG3 antibodies in combination with the H/H131 genotype was observed. Furthermore, low levels of IgG2 antibodies reactive with the Pf332-C231 antigen were also associated with lower risk of severe malaria in individuals carrying the H131 allele. The levels of IgG1 and IgG3 antibodies were statistically significantly higher in the mild malaria patients when compared with the severe malaria patients. Taken together, our study revealed that the FcgammaRIIa-R/R131 genotype is associated with the development of severe malaria, while the H/H131 genotype is more likely to be associated with mild malaria. Our results also revealed that the natural acquisition of immunity against clinical malaria appeared to be more associated with IgG1 and IgG3 antibodies, signifying their roles in parasite-neutralizing immune mechanisms.