Prevalence of depression among people living with HIV in rural hospitals in South-Western Nigeria-Association with clinico-demographic factors.

Major depression is the most common neuropsychiatric disorder among people living with HIV (PLWH) and is predictive of high morbidity and mortality among them. This study estimated the prevalence and explored factors associated with depression among PLWH in two rural secondary health facilities providing anti-retroviral therapy (ART) services in Southwestern Nigeria between September and December 2020. The Patient Health Questionnaire-9 (PHQ-9) was used to screen and identify PLWH aged 18 years or older with depression. Descriptive statistics, bivariate and multivariate analyses were performed with SPSS version 23. A total of 172 respondents were screened. The prevalence of depression was 16.3% (95% CI 11.1%, 22.7%). Mild, moderate, and moderately severe depression was identified in 17 (9.9%), 8(4.7%) and 3(1.7%) of the participants, respectively. One (0.6%) respondent had suicidal ideation. Of PLWH with any depression, 20/28(71.4%) were within the 40-59 years of age range. None of the participants was on antidepressants. The factor most associated with depression was hypertension, with adjusted odd ratios of 9.8(95% CI 3.5-27.3, p < 0.0001). The study highlights the importance of screening for the severity of depression among PLWH in rural hospitals providing ART services in Africa. PLWH with comorbid hypertension were more likely to suffer from some form of depression.

Differential effects of carbamazepine and levetiracetam monotherapy on reproductive endocrine function in Nigerian women with epilepsy.

Objective: This study is aimed at comparing differential effect of Levetiracetam (LTC) monotherapy and Carbamazepine (CZP) monotherapy in W omen with epilepsy (WWE) on gonadal hormone. Methods: 87 WWE were recruited comprising randomly of 46 and 41 on CZP and LTC group respectively with diagnosis and classification based on International League Against Epilepsy (ILAE). Reproductive hormones (Luteinizing Hormone (LH), Follicle stimulating hormone, progesterone, estradiol and testosterone) were assayed. National Hospital Seizure Severity Scale (NHSS) and Zung self-reporting depression scale (ZSRDS) were used to assess the seizure severity and the mood respectively. Data was analyzed using Statistical Package for Social Sciences (SPSS) version 20. The Chi-square test was used to compare categorical variables while Student's t-test or its non-parametric equivalent where appropriate were used to compare continuous variables. Results: Clinical characteristics were comparable in both groups except for ZSRDS (p = 0.048), NHSS (p = 0.012) and hip circumference (p = 0.037). The CZP group had a higher ASEX score and proportion of WWE with clinically significant sexual dysfunction (p < 0.001). WWE on LTC had similar hormonal profiles with those on CZP except for a higher median serum testosterone level (p = 0.004), and lower median serum LH (p = 0.006). Age was negatively associated with serum testosterone level for the 25th, 50th, and 75th quartile. However, the differential effect for AED type was only significant for the 25th quartile; with higher values in LTC. Conclusion: The therapeutics implication of lower LH and testosterone levels in the LTC group compared to CZP group need to be explored.

Pattern and predictors of medication use among adults in southwestern Nigeria: A community-based cross-sectional study.

Population-based drug utilization studies are scanty in Nigeria. The aim was to determine the pattern and predictors of medication use among adults in the communities of Southwestern Nigeria. A cross-sectional study was conducted among adults selected by multi-stage sampling from Oyo State communities. The questionnaires, adapted from the WHO Students' Drug Use Questionnaire and previous studies, were pretested and interviewer administered. The respondents' socio-demographic characteristics, the pattern of medication use, prescribers, and sources of drug acquisition were obtained. Binary logistic regression was used to determine the predictor of medications used. Of the 999 respondents, 501 resided in rural communities while 498 dwelled in urban areas. The mean (±SD) age of the respondents was 38 ± 15 years. The median (range)% prevalence of medication use were as follows: lifetime use, 58.2 (17.7-81.0); current use, 31.2 (8.9-65.9); and past use, 20.3 (9.2-28.9). Medications were mainly obtained from patent medicine stores, median (range%), 71 (65-80). The commonly used drugs were paracetamol, 626 (67.6); nonsteroidal anti-inflammatory drugs, 174 (18.8); artemether/lumefantrine, 422 (68.2); ampicillin/cloxacillin, 220 (48.6); and chlorpheniramine, 59 (39.9). Factors predictive of current medication use, adjusted odd ratio (95% confidence interval) were as follows: antimalarial [male, 0.7 (0.5, 0.9)]; antibacterial [male, 0.6 (0.4-0.9)]; analgesics [married, 1.5 (1.1-2.2); presence of health facilities, 0.5 (0.3-0.7); and shorter distance to health facility, 1.5 (1.1-2.1)]. Antimalarials, antibacterial, and analgesics were commonly used and inappropriately obtained by adults in Southwestern Nigeria. Factors predictive of current medication use were gender, marital status, the presence of health facilities, and distance to health facilities. There is a need for more extensive countrywide medication use studies and enlightenment programs to ensure the appropriate use of medications.

Adverse drug reactions reporting practice and associated factors among community health extension workers in public health facilities, Southwest, Nigeria.

INTRODUCTION: timely adverse drug reactions (ADRs) reporting has contributed immensely towards public health safety. Community health extension workers (CHEWs) provides basic medical care in rural areas. This study assessed the knowledge, attitude, practice, and determinants of ADRs reporting among CHEWs in public health institutions, Southwest, Nigeria. METHODS: a cross-sectional survey of 333 CHEWs randomly selected from public health facilities using self-administered questionnaires. The questionnaire sought information on the knowledge, attitude and practice of CHEWs towards ADRs reporting. The knowledge and attitude questions were scored and categorized. The association between dependent and independent variables assessed with bivariate and multivariate logistic regressions, and p < 0.05 considered statistically significant. RESULTS: among 333 respondents, 205 (61.6%) had encountered patients with ADRs but only 26 (12.6%) had reported it with yellow forms. About half, 169 (50.8%), and 191 (57.4%) respondents had a positive attitude and inadequate knowledge of ADRs reporting respectively. Sex (aOR: 2.84, 95% CI: 2.10-7.10; p < 0.0001), working in Ogbomoso area (aOR: 3.3, 95% CI: 1.34-8.21; p=0.01), and training (aOR: 2.01, 95% CI: 1.20-3.42; p = 0.01) were factors associated with adequate knowledge. The determinant of ADRs reporting was training (aOR: 3.63, 95% CI: 1.13-11.63; p = 0.03). CONCLUSION: though CHEWs had a slightly positive attitude, they had inadequate knowledge and poor ADRs reporting. The determinant of inadequate ADRs reporting knowledge and under reporting was lack of training. There is an urgent need for educational intervention programmes towards improving knowledge and practices of ADRs reporting among CHEWs.

Malaria burden and pre-hospital medication among subjects with malaria in Maiduguri, Northeast Nigeria.

The study re-visited malaria burden and pre-hospital medication among malarious subjects in Maiduguri, Northeast Nigeria. A total of 1,657 febrile subjects were screened for malaria by microscopy at two health institutions. Giemsa-stained blood smears were examined for parasitaemia and gametocytaemia; and parasite density (PD), gametocyte density (GD) and gametocyte sex ratio (GSR) were determined. The mean age of the 1,657 subjects was 27.5 ± 12.2 years and 7.8% (130/1,657) of the subjects aged <5 years. Sex distribution showed 47.0% (778/1,657) males and 53.0% (879/1657) females. Parasitaemia was recorded in 22.6% (375/1,657) with geometric mean PD of 8,925 (320-275,000) parasites/µl blood. The prevalence of parasitaemia was highest among subjects <5 years (χ2 = 401.1; df = 5; p < 0.0001) and in August and September (χ2 = 406.9; df = 11; p < 0.0001). Prevalence of gametocytaemia was 12.8% (48/375) with geometric mean GD of 109 (8-464) gametocytes/µl blood. The prevalence was higher in dry (16.5%, 29/176) than wet (9.5%, 19/199) months (χ2 = 4.0; df = 1; p = 0.045). The weighted mean GSR was 0.4 ± 0.1 with highest value in March (0.7 ± 0.2). Pre-hospital medication was recorded in 74.1% (278/375) of the subjects with parasitaemia. Analgesics (51.7%; 194/375) accounted for the highest proportion of drug consumed while 9.3% (35/375) of the subjects took antimalarial drugs. Malaria persisted in Maiduguri especially among subjects <5 years during wet months and pre-hospital medication is a common practice. These findings could serve as guide for policy decision that could contribute to effective treatment and control of malaria in the region.

Evaluation of CYP2D6 phenotype in the Yoruba Nigerian population.

BACKGROUND: There is a lack of information on CYP2D6, a major metabolizing enzyme, in Africa ethnic nationalities. The objective was to determine CYP2D6 phenotype in Yoruba Nigerians using dextromethorphan (DEX). METHOD: A total of 89 healthy volunteers received 30 mg of DEX orally followed by blood and urine sample collection at 3-hour and over 8 h post-dose, respectively. DEX and dextrorphan (DOR) concentrations were determined using High Performance Liquid Chromatography (HPLC). The metabolic ratio (MR, DEX/DOR) were plotted for the phenotype determination. RESULTS: The log MR that separated poor (PMs) from normal metabolizers (NMs) was 0.28 and 0.75 for urine and plasma, respectively. Two subjects (2.3%) identified as PMs had a mean MR of 17 and 3.2 in plasma and urine, significantly higher than that of NMs (p < .0001). A positive correlation between urine and plasma MR was noted. CONCLUSION: The prevalence of PMs in the Yoruba Nigerians was similar to that reported among blacks.

A comparative study of azithromycin and sulphadoxine-pyrimethamine as prophylaxis against malaria in pregnancy.

CONTEXT: The benefit of malaria prophylaxis in pregnancy is threatened by emergence of Plasmodium falciparum resistance to antimalarial agents for chemoprophylaxis and treatment. AIM: This study aimed to compare the effectiveness of azithromycin (AZ) with sulphadoxine-pyrimethamine (SP) for malaria prevention. SETTINGS AND DESIGN: A prospective comparative study of antenatal clinic attendees at the University College Hospital, Ibadan, Nigeria. Participants were randomised to receive SP or AZ. SUBJECTS AND METHODS: The subjects were antenatal attendees and Samples for malaria parasitaemia were collected and repeated at follow-up visits; maternal peripheral blood film, placental and cord blood samples were collected at delivery. STATISTICAL ANALYSIS USED: Chi-square test and t-test in a per-protocol analysis. RESULTS: Of 200 participants (100 in each group), 166 (83.0%) completed the study: 86 (86.0%) of SP and 80 (80.0%) of AZ groups, respectively (P = 0.26). Four (4.7%) participants who had SP compared to five (6.2%) in AZ group developed malaria at mean gestational ages of 30.3 ± 1.56 and 33.0 ± 8.6, respectively (P = 0.56). Positive peripheral, placental and cord blood parasitaemia were found in ≤2% of the participants. Drug tolerability and foetal outcomes were comparable for both groups. CONCLUSION: AZ was comparable to SP for prevention of malaria in pregnancy and may be used in patients who do not tolerate SP.

In vitro sensitivity of Plasmodium falciparum clinical isolates to 4-aminoquinolines in Northeast Nigeria.

Background: Widespread dr ug-resistant Plasmodium falciparum strains have challenged the pivotal role played by 4-aminoquinolines, including chloroquine (CQ), which has been delisted for the treatment of malaria in most parts of the world. This study assessed the in vitro sensitivity of P. falciparum clinical isolates (PfCIs) to amodiaquine (AQ) and CQ in Northeast Nigeria. Materials and methods: PfCIs were collected from subjects with uncomplicated P. falciparum malaria in Azare, Bauchi State and Maiduguri, Borno State following an informed consent. The in vitro sensitivity was assessed by micro-test (MarkIII) method and the IC50 of AQ and CQ was determined using HN-NonLin Version VI.1 software. The reference standard cut-off values for in vitro AQ and CQ resistance of 80 and 160 nmol/l, respectively, were used. Isolates that were inhibited by lower AQ and CQ concentrations were referred to as sensitive. Results: Valid in vitro assay r esults were obtained for 88.9% (80/90) of the PfCIs; Azare had 93.3% (28/30) and Maiduguri had 86.7% (52/60) [χ2 = 0.35; df = 1; p = 0.486]. The geometric mean (GM) IC50 of AQ and CQ were 24.2 nmol/l (95% CI, 10.5 - 49.6 nmol/l) and 39.5 nmol/l (95% CI, 34.5 - 49.6 nmol/l), respectively. The AQ (p = 0.922) and CQ (p = 0.085) GM IC50 were similar between Azare and Maiduguri PfCIs. Only one isolate showed in vitro resistance to AQ giving a sensitivity of 98.8% (79/80) while 17 PfCIs showed in vitro resistance to CQ giving a sensitivity of 78.8% (63/80). The CQ sensitivity was similar between Azare (67.9%; 19/28) and Maiduguri (84.6%; 44/52) PfCIs (χ2 = 3.05; df = 1; p = 0.081). Conclusions: The findings may suggest that the AQ in vitro sensitivity remains high and the isolates in Northeast Nigeria may appear more sensitive to CQ than isolates from other parts. These findings may affect malaria treatment and control policy in Nigeria.

Artemether-Lumefantrine Exposure in HIV-Infected Nigerian Subjects on Nevirapine-Containing Antiretroviral Therapy.

Coadministration of nevirapine-based antiretroviral therapy (ART) and artemether-lumefantrine is reported to result in variable changes in lumefantrine exposure. We conducted an intensive pharmacokinetic study with 11 HIV-infected adults who were receiving artemether-lumefantrine plus nevirapine-based ART, and we compared the results with those for 16 HIV-negative adult historical controls. Exposure to artemether and lumefantrine was significantly lower and dihydroartemisinin exposure was unchanged in subjects receiving nevirapine-based ART, compared with controls. Nevirapine exposure was unchanged before and after artemether-lumefantrine administration.

Asymptomatic falciparum malaria and genetic polymorphisms of Pfcrt K76T and Pfmdr1 N86Y among almajirai in northeast Nigeria.

INTRODUCTION: Malaria remains a public health challenge, especially in sub-Saharan Africa where asymptomatic malaria is not uncommon. In the present study, the prevalence of asymptomatic falciparum malaria was investigated in almajirai, and the genetic polymorphisms of chloroquine (CQ) resistance biomarkers were assessed. METHODOLOGY: A total of 440 apparently healthy almajirai between 3 and 12 years of age were randomly enrolled in Maiduguri, northeast Nigeria, between July and December 2010. Parasitemia and gametocytemia were assessed by light microscopy, and polymorphisms of Pfcrt K76T and Pfmdr1 N86Y were detected by nested polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. RESULTS: The mean age of the subjects was 8.3 ± 4.5 years, with subjects ≤ 5 years accounting for 10.7% (47/440) of the population. Prevalence of asymptomatic falciparum parasitemia and gametocytemia were 12.7% (56/440) and 8.6% (38/440), respectively. Geometric mean parasite density (GMPD) was 240 (160-630) parasites/µL, while geometric mean gametocyte density (GMGD) was 53 (24-96) gametocytes/µL. The GMPD was higher among subjects ≤ 5 years of age (p = 0.027). Pfcrt 76T was detected in 5.4% (3/56) of the isolates, and no isolates harbored Pfmdr1 86Y mutant. CONCLUSIONS: The study reveals asymptomatic falciparum malaria in almajirai and low levels of Pfcrt 76T and Pfmdr1 86Y alleles. These findings could hinder malaria control measures, and hence almajirai should be incorporated into malaria control programs.

Disposition of amodiaquine and desethylamodiaquine in HIV-infected Nigerian subjects on nevirapine-containing antiretroviral therapy.

OBJECTIVES: Artesunate plus amodiaquine is used for malaria treatment in regions with overlapping HIV endemicity. Co-administration of artesunate/amodiaquine with antiretroviral therapy (ART) may result in drug-drug interactions, but minimal data exist. This study evaluated the impact of nevirapine-based ART, containing a backbone of zidovudine and lamivudine, on the disposition of amodiaquine and its active metabolite, desethylamodiaquine (DEAQ). METHODS: This was an open-label, parallel-group pharmacokinetic comparison between HIV-infected, adult subjects receiving steady-state nevirapine-based ART (n = 10) and ART-naive subjects (control group, n = 11). All subjects received a loose formulation of artesunate/amodiaquine (200/600 mg) daily for 3 days, with serial pharmacokinetic sampling over 96 h following the final dose of artesunate/amodiaquine. Amodiaquine and DEAQ were quantified using a validated HPLC method with UV detection. Pharmacokinetic parameters were determined using standard non-compartmental methods. RESULTS: Exposures to both amodiaquine and DEAQ were significantly lower in the nevirapine-based ART group compared with the control group (amodiaquine AUC0₋24 145 versus 204 ng·h/mL, P = 0.02; DEAQ AUC0₋96 14,571 versus 21,648 ng·h/mL, P < 0.01). The AUCDEAQ/AUC(amodiaquine) ratio was not different between groups (ART group 116 versus control group 102, P = 0.67). CONCLUSIONS: Subjects on nevirapine-based ART had lower exposure to both amodiaquine and DEAQ (28.9% and 32.7%, respectively). Consequently, this may negatively impact the effectiveness of artesunate/amodiaquine in HIV-infected individuals on this ART combination.

Nevirapine-Based Antiretroviral Therapy Impacts Artesunate and Dihydroartemisinin Disposition in HIV-Infected Nigerian Adults.

Background. Nevirapine- (NVP-) based antiretroviral therapy (ART) and artesunate-amodiaquine are frequently coprescribed in areas of HIV and malaria endemicity. We explored the impact of this practice on artesunate and dihydroartemisinin pharmacokinetics. Methods. We conducted a parallel-group pharmacokinetic comparison between HIV-infected patients receiving NVP-based ART (n = 10) and ART-naive controls (n = 11). Artesunate-amodiaquine 200/600 mg was given daily for three days. Measurement of drug concentrations occurred between 0 and 96 hours after the final dose. Pharmacokinetic parameters were determined using noncompartmental analysis. Results. Comparing the NVP group to controls, clearance of artesunate was reduced 50% (1950 versus 2995 L/h; P = 0.03), resulting in a 45% increase in the AUC(0-96) (105 versus 69 ug(∗)hr/L; P = 0.02). The half-life of dihydroartemisinin was shorter in the NVP group (1.6 versuss 3.2 h; P = 0.004), but other dihydroartemisinin pharmacokinetic parameters were unchanged. A lower conversion of artesunate to dihydroartemisinin was observed in the NVP group (dihydroartemisinin: artesunate AUC(0-96) = 5.6 versuss 8.5 in NVP and control groups, respectively, P = 0.008). Conclusion. Although NVP-containing ART impacted some pharmacokinetic parameters of artesunate and dihydroartemisinin, overall exposure was similar or better in the NVP group.

Correlation between plasma levels of radical scavengers and hearing threshold among elderly subjects with age-related hearing loss.

CONCLUSION: Low plasma melatonin is significant in the development of high frequency hearing loss (HL) among the elderly. OBJECTIVE: To determine the correlation between hearing threshold and the plasma melatonin and ascorbic acid (vitamin C). METHODS: This was a cross-sectional study involving 126 apparently healthy elderly subjects, 59 males and 67 females, aged >60 years. Subjects underwent pure tone audiometry and plasma melatonin and vitamin C were assayed using high-performance liquid chromatography. RESULTS: The mean ± SD of plasma melatonin among the subjects with normal hearing (NH) (0-30 dB) and those with HL in the speech frequencies was 18.3 ± 3.6 µg/L and 16.4 ± 4.7 µg/L, respectively. In the high frequencies the values were 17.7 ± 6.2 µg/L and 13.1 ± 6.4 µg/L for NH and HL, respectively. For vitamin C, the mean ± SD among subjects with NH and those with HL in the speech frequencies were 1.2 ± 0.2 µg/L and 1.0 ± 0.1 µg/L, respectively. In the high frequencies, the values were 1.0 ± 0.2 µg/L and 0.9 ± 0.3 µg/L for NH and HL, respectively. Among subjects with high frequency HL, Spearman's correlation revealed significant correlation between increasing hearing threshold and melatonin (correlation coefficient = -0.30, p = 0.01), but not for vitamin C (correlation coefficient = -0.12, p = 0.22). Linear regression, adjusting for age, still revealed significant correlation between the melatonin (correlation coefficient = -0.03, p = 0.00) and hearing threshold in the high frequencies.

Exposure to anti-malarial drugs and monitoring of adverse drug reactions using toll-free mobile phone calls in private retail sector in Sagamu, Nigeria: implications for pharmacovigilance.

BACKGROUND: Adverse drug reactions (ADRs) contribute to ill-health or life-threatening outcomes of therapy during management of infectious diseases. The exposure to anti-malarial and use of mobile phone technology to report ADRs following drug exposures were investigated in Sagamu--a peri-urban community in Southwest Nigeria. METHODS: Purchase of medicines was actively monitored for 28 days in three Community Pharmacies (CP) and four Patent and Proprietary Medicine Stores (PPMS) in the community. Information on experience of ADRs was obtained by telephone from 100 volunteers who purchased anti-malarials during the 28-day period. RESULTS AND DISCUSSION: A total of 12,093 purchases were recorded during the period. Antibiotics, analgesics, vitamins and anti-malarials were the most frequently purchased medicines. A total of 1,500 complete courses of anti-malarials were purchased (12.4% of total purchases); of this number, purchases of sulphadoxine-pyrimethamine (SP) and chloroquine (CQ) were highest (39.3 and 25.2% respectively). Other anti-malarials purchased were artesunate monotherapy (AS)--16.1%, artemether-lumefantrine (AL) 10.0%, amodiaquine (AQ)--6.6%, quinine (QNN)--1.9%, halofantrine (HF)--0.2% and proguanil (PR)--0.2%. CQ was the cheapest (USD 0.3) and halofantrine the most expensive (USD 7.7). AL was 15.6 times ($4.68) more expensive than CQ. The response to mobile phone monitoring of ADRs was 57% in the first 24 hours (day 1) after purchase and decreased to 33% by day 4. Participants in this monitoring exercise were mostly with low level of education (54%). CONCLUSION: The findings from this study indicate that ineffective anti-malaria medicines including monotherapies remain widely available and are frequently purchased in the study area. Cost may be a factor in the continued use of ineffective monotherapies. Availability of a toll-free telephone line may facilitate pharmacovigilance and follow up of response to medicines in a resource-poor setting.

Correlation between serum immunoglobulin G and hearing threshold among elderly subjects with age-related hearing loss.

BACKGROUND AND PURPOSE: This study was based on the hypothesis that suboptimal immune response and low serum immunoglobulin G (IgG) may predispose to age-related hearing loss (ARHL), and the objective was to determine the serum levels of IgG and hearing thresholds of apparently healthy elderly subjects and assess their correlation. METHOD: This prospective study involved 126 participants ≥ 60 years old who were found to be free of any medical conditions. Pure-tone averages for both the speech (500-2,000 Hz) and high frequencies (3,000-8,000 Hz) and serum IgG levels were determined. Using 30 dB as cut-off for hearing loss, the correlation with serum IgG was assessed. RESULTS: There were 59 males and 67 females with a mean age ± SD of 67.0 ± 2.7 years. Speech frequency hearing loss was seen in 30.2%, while high-frequency hearing loss accounted for 74.6%. In the speech frequencies, the mean ± SD of serum IgG among subjects with normal hearing was 11.3 ± 3.9 g/l, while among those with hearing loss it was 8.3 ± 3.3 g/l (p = 0.01). In the high frequencies, the mean ± SD values of serum IgG among the subjects with normal hearing was 11.1 ± 2.3 g/l, while among those with hearing loss it was 8.7 ± 1.9 g/l (p = 0.01). CONCLUSION: Low serum IgG may be a contributory factor to the development of ARHL among the elderly. However, a longitudinal study involving intervention with immunoglobulin supplementation may further confirm this role.

Drug interactions in the treatment and chemoprophylaxis of malaria in HIV infected individuals in sub Saharan Africa.

Malaria and HIV/AIDS remain diseases of public health importance in sub-Saharan Africa as both infections are responsible for high morbidity and mortality rates. Malaria disproportionately affects young children and pregnant women and HIV/AIDS affects mostly adolescents and young adults. The widespread nature of both infections has led to co-infection in many residents of sub-Saharan African countries. HIV-infected individuals are more susceptible to frequent attacks of malaria thus requiring combination antiretroviral therapy and antimalarial drugs. There is, in general, lack of information on the influence of the chronic use of antiretroviral medicines on the outcome of repeated treatment of malaria. Pharmacokinetic drug interactions with HIV medications that lead to sub-therapeutic concentrations of antimalarial drugs will promote drug resistance in patients with malaria. The objective of this review is to summarize the available information on the adverse drug reactions and drug interactions of commonly used antimalarial drugs in the context of combination antiretroviral therapy and propose a clinical pharmacology research plan to develop dosing recommendations for patients with malaria and HIV co-infection.

Age-related hearing loss, vitamin B12, and folate in the elderly.

OBJECTIVE: Determine the correlation between the hearing threshold and the serum levels of vitamin B12 (cobalamin) and folic acid among elderly subjects (> 60 years) with age-related hearing loss (ARHL). STUDY DESIGN: Cross-sectional. SETTING: Community. SUBJECTS AND METHODS: Subjects included elderly who were found apparently healthy following repeated examination by physicians. The pure tone average (PTA) for the speech and high frequencies, and the serum folate and cobalamin were determined and the correlation found. RESULTS: The mean ± SD values of serum folate among the subjects with normal PTA in the speech frequencies (0-30 dB) was 412.3 nmol/L ± 17.6 nmol/L, while among those with hearing loss (HL), it was 279.1 nmol/L ± 17.2 nmol/L (P = 0.01). In the high frequencies, the mean ± SD values among the subjects with normal PTA was 426.3 nmol/L ± 17.6 nmol/L, while among those with HL, it was 279.14 nmol/L ± 171.2 nmol/L. The serum cobalamin among the subjects with normal PTA within the speech frequencies was 49.7 pmol/L ± 9.4 pmol/L, while among those with speech-frequency HL, it was 42.6 pmol/L ± 10.2 pmol/L. However, for high frequencies, the mean ± SD values among the subjects with normal PTA was 47.4 pmol/L ± 7.3 pmol/L, while among those with HL, it was 41.3 pmol/L ± 9.2 pmol/L. Spearman's correlation revealed that low folate (correlation coefficient = -0.27, P = 0.01) and cyanocobalamin (correlation coefficient = -0.35, P = 0.02) were significantly associated with increasing hearing threshold in the high frequencies. After adjusting for age, serum folate (correlation coefficient = -0.01, P = 0.01) was significant, while vitamin B12 (correlation coefficient = -0.01, P = 0.74) was not. CONCLUSION: Serum folate was significantly lower among elderly with ARHL. Trials on nutritional supplementation may substantiate the role of serum folate in ARHL.

Activities of artemether-lumefantrine and amodiaquine-sulfalene-pyrimethamine against sexual-stage parasites in falciparum malaria in children.

The activities of artemether-lumefantrine and amodiaquine-sulfalene-pyrimethamine against sexual-stage parasites were evaluated in 42 of 181 Nigerian children with uncomplicated Plasmodium falciparum malaria who had gametocytaemia before, during or after treatment with the two combination therapies. The children were randomized to the standard dose regimens. Clinical recovery from illness occurred in all children who carried gametocytes. Gametocytaemia was detected in 20 patients (11%) before treatment and in another 22 patients (12.2%) after treatment. Gametocyte carriage rates were similar in both combination treatment groups, but the area under the curve of gametocytaemia plotted against time was 8-fold higher in the amodiaquine-sulfalene-pyrimethamine-treated than in the artemether-lumefantrine-treated children. The pretreatment gametocyte sex ratio was female biased in both treatment groups. During follow-up, there was a short-lived but significant increase in the gametocyte sex ratio in children treated with amodiaquine-sulfalene-pyrimethamine but not in those treated with artemether-lumefantrine. These results indicate that both combination therapies had moderate effects on gametocyte carriage, but artemether-lumefantrine may be more potent at reducing transmissibility in P. falciparum malaria by exerting greater effects on post-treatment gametocyte density and gametocyte sex ratio.

Effects of artesunate-cotrimoxazole and amodiaquine-artesunate against asexual and sexual stages of Plasmodium falciparum malaria in Nigerian children.

The activities of artesunate-cotrimoxazole and artesunate-amodiaquine combinations against asexual-and sexual-stage parasites were evaluated in 182 Nigerian children with uncomplicated Plasmodium falciparum malaria. One hundred and twenty-one children received artesunate-cotrimoxazole and 61 received artesunate-amodiaquine and all were followed up for 28 days. Clinical recovery from illness occurred in all children. There was no significant difference in fever clearance time (P = 0.35). Both treatment groups achieved a parasite clearance time of less than 2 days (1.84 +/- 0.66 days and 1.31 +/- 0.48 days); gametocyte carriage rates were comparable in the two treatment groups prior to and following treatment; both treatments appeared to reduce gametocyte carriage. The pretreatment gametocyte sex ratio, which was female-biased, was maintained throughout the period of follow up in both treatment groups. Reduction of gametocyte carriage by these two treatment regimens may reduce transmissibility in P. falciparum malaria, and this reduction is presumed to be related to the accelerated clearance of the asexual forms of the parasite.