Antimalarial drug resistance markers in human immunodeficiency virus (HIV)-positive and HIV-negative adults with asymptomatic malaria infections in Port Harcourt, Nigeria.

BACKGROUND: In Nigeria, indiscriminate use of antimalarial drugs may contribute to the threat of drug resistance, but this has not been evaluated among people living with human immunodeficiency virus (HIV). METHODS: HIV-positive adults attending a university hospital HIV clinic and HIV-negative adult volunteers from the university hospital community with a positive blood film were treated with artemether-lumefantrine. Parasite DNA from before and after treatment was polymerase chain reaction amplified to identify molecular markers of drug susceptibility. RESULTS: The pfcrt76T genotype was prevalent among both HIV-positive and HIV-negative participants (78.6% and 68.2%, respectively). Three new mutations in the pfmdr1 gene-F73S, S97L and G165R-and the uncommon pfdhps S436F variant were detected, whereas pfdhps K540E and pfdhfr I164L were absent. The A437G allele of pfdhps predominated (62/66 [94%]). The I431 V mutation was found in 19 of 66 pretreatment pfdhps sequences (28.8%). The pfmdr1 86N allele was significantly more common at day 3 post-treatment than at baseline (odds ratio 8.77 [95% confidence interval 1.21 to 380]). CONCLUSIONS: We found evidence of continued chloroquine use among HIV-positive individuals. Selection for the pfmdr1 86N after artemether-lumefantrine treatment was observed, indicating a possible threat to antimalarial efficacy in the study area. The complexity of pfdhps haplotypes emphasises the need for careful monitoring of anti-folate susceptibility in Nigeria

HIV-positive nigerian adults harbor significantly higher serum lumefantrine levels than HIV-negative individuals seven days after treatment for Plasmodium falciparum infection.

Management of coinfection with malaria and HIV is a major challenge to public health in developing countries, and yet potential drug-drug interactions between antimalarial and antiviral regimens have not been adequately investigated in people with both infections. Each of the constituent components of artemether-lumefantrine, the first-line regimen for malaria treatment in Nigeria, and nevirapine, a major component of highly active antiretroviral therapy, are drugs metabolized by the cytochrome P450 3A4 isoenzyme system, which is also known to be induced by nevirapine. We examined potential interactions between lumefantrine and nevirapine in 68 HIV-positive adults, all of whom were diagnosed with asymptomatic Plasmodium falciparum infections by microscopy. Post hoc PCR analysis confirmed the presence of P. falciparum in only a minority of participants. Day 7 capillary blood levels of lumefantrine were significantly higher in HIV-positive participants than in 99 HIV-negative controls (P = 0.0011). Associations between day 7 levels of lumefantrine and risk of persistent parasitemia could not be evaluated due to inadequate power. Further investigations of the impact of nevirapine on in vivo malaria treatment outcomes in HIV-infected patients are thus needed

Adherence to Antiretroviral Therapy Among HIV-infected Subjects in a Resource - limited Setting in the Niger Delta of Nigeria

Since the early days of antiretroviral therapy, adherence has emerged a milestone to success. The objective of this study was to evaluate the factors militating against adherence to antiretroviral therapy among HIV-infected individuals in the resource - limited setting of the Niger Delta of Nigeria. A structured interviewer- administered questionnaire from consecutively recruited 187 HIV-infected patients on combination antiretroviral therapy of two-nucleoside analogue; stavudine and lamivudine and one non-nucleoside (nevirapine) was used. Association between the independent variables and adherence were analyzed using chi square analysis. This study observed an adherence level of 49.2% and identified the following as factors associated with nonadherence: cost of antiretrovirals, educational status, medication adverse effect, occupational factors, and high pill burden of prescribed regimen (p < 0.05). There is an urgent need for universal access and sustainability of antiretroviral therapy particularly in resource - limited settings. There is need for supervised medication delivery. Efforts should be made towards simplifying the therapeutic regimen to reduce the pill burden and substitution with treatment combination and strategies that minimize negative adverse effects, coupled with the re-intensification of patient's education and counseling

Use of artemether-lumefantrine in the treatment of asymptomatic-malaria infection in HIV-positive and HIVnegative Nigerian adults.

Malaria /HIV co-infection is a major challenge to public health in developing countries and yet potential drug-drug interactions between antimalarial and antiviral regimens have not been adequately investigated in people with both HIV and Plasmodium falciparum infections. Earlier studies on the use of artemether-lumefantrine (AL) in Nigeria have neither addressed its use in HIV-positive subjects nor in asymptomatic-malaria infection. The present study investigated associations between drug resistant P. falciparum and the use of medication for HIV management, drug-drug interactions between artemether-lumefantrine and antiretroviral drugs (ARV) and the molecular markers of artemether-lumefantrine and other antimalarial drugs. Results of the study revealed an elevated day 7 lumefantrine concentrations in HIV subjects on nevirapine treatment compared to their HIV-negative counterparts. Associations between elevated day 7 levels of lumefantrine and the persistent parasitaemia could not be evaluated due to inadequate power. Genetic analysis by DNA sequence of P. falciparum isolates revealed strong selection for the pfmdr1codon86N allele among all treated individuals. This polymorphism is a strong indicator of AL treatment failure or slow clearance in vivo. There was a 72.6% prevalence of the pfcrt76T mutations in the population and this was observed to be higher in the HIV-positive subjects. Three new mutations F73S, S97L and G165R were detected on the pfmdr1 gene and the first case S436F mutation on the pfdhps gene to be reported in Nigeria. The dhpsK540E and dhfrI164L mutations, associated with high-level resistance to sulfadoxine-pyrimethamine (SP) were not observed in our small sample size. The study also revealed that HIV-positive subjects were more likely to harbour parasites, at a higher density, before and after treatment. Improvement of the immune status of HIV-infected patients was suggested by the increase of CD4 cell count level in about 68% of the HIV-positive patients. This is a preliminary study and first of its kind to investigate drug-drug interactions between ARVs and the antimalarial drug AL in HIV-positive patients co-infected with P. falciparum in relation to parasite clearance. The findings of the study are very important but more work is urgently needed with a larger sample size to confirm these findings

Malaria/HIV Interactions in Nigeria - A Review

Background: Malaria and HIV are two of the most common and important health problems facing developing countries and Nigeria being the most populous African country bears a very high percentage of this burden. This article is an attempt to review the published articles on the coinfection of the two diseases available in literature from Nigeria.Methods: A review of the literature on the subject was done utilizing google search, Medline, PubMed and other available literature. The keywords were Malaria andHIV; Interactions and Nigeria.Results: Malaria and HIV constitute major public health threats responsible for significant morbidity and mortality in the country. Malaria and HIV are diseases of poverty resulting in over 4 million deaths a year. Both diseases are highly endemic, with a wide geographic overlap in sub-Saharan Africa and Nigeria. The management of the co-infection is a major challenge to the public health system. Of particular importance is the potential drug-drug interactions involved in the management of the co-infections as a result of coadministration of the drugs which have not been adequately investigated.Conclusion: Despite the endemicity of both diseases in Nigeria, there is paucity of data on the interaction of the two diseases.Keywords: Malaria; HIVIAIDS; Coinfection; Nigeria; Revie

ABO and Rhesus blood groups in mothers and their newborns in Port Harcourt, Nigeria

Background: Blood groups are inheritable red cell antigens passed on to the next generation in a simple Mendelian pattern. The distribution of blood group antigens is fairly constant in a given population. They are therefore important in the planning of blood transfusion services and anthropology.Aim: To ascertain the distribution of ABO and Rhesus (Rh) red cell antigens in mothers and their newborns, and examine the risk of ABO and Rh incompatibility in Port Harcourt, Nigeria.Methods: A total of 103 women in their immediate post-partum state and their newborns were randomly recruited into the study. The study was conducted between October and December 2004. Blood samples from mothers and babies were analyzed for ABO and Rh D red cell antigens.Results: ABO antigens were distributed as follows: Mothers, group O 58.2%, group A (22.3%), group B (16.5%) and AB (2.9%). In babies:  group O (65.1%), group A (19.4%), group B (13.6%) and group AB (1.9%). Rh D antigen was positive in 95.2% of mothers and 94.2% of babies. Eight (7.7%) of the maternal-cord blood pairs had a possible risk of ABO incompatibility. Only two babies had haemoglobin concentration (Hb) less than 10.0g/dl. Three (2.9%) of the maternal-cord blood pairs had a possible risk of Rh D incompatibility, but all three babies had Hb≥ 14.0g/dl.Conclusion: This study  shows that blood group O was by far the commonest ABO blood group in mothers and their babies in the Port Harcourt area. Rh D positivity was about 95% in both groups. Therefore, blood group O, Rh positive blood should constitute the main group in the blood banks in this area. The overall risk of ABO and Rh D incompatibility between mother and child was low in this study.Keywords: ABO, Rhesus, Blood groups, Mothers, Newborn

Assessment of treatment pattern of uncomplicated malaria in under-fives in a paediatric unit of a Nigerian tertiary hospital

Malaria remains a very important health challenge in Nigeria, particularly among children under five years of age. Definitive diagnosis is very necessary in order to ensure appropriate treatment of malaria in this vulnerable group. The study examined the diagnosis and treatment pattern of uncomplicated malaria in under-five children in the Paediatric Unit of the University of Port Harcourt Teaching Hospital (UPTH) for the period between January 2014-January, 2016. Five hundred case notes of the children who were treated from January 2014-January 2016 were examined. Data extracted include the diagnostic procedure, screening and laboratory investigation, and the pattern of prescription of antimalarial drugs in addition to the demographic information of the patients. Co-morbidities associated with malaria as well as coprescribed drugs were also investigated. Results obtained show that only 30.8% (154) of the diagnosis were based on microscopic examination of thick/thin blood film of malaria parasites. ACT drugs were found to be prescribed in 62.4% cases while the rest (37.6%) were non-ACT drugs. The prescribing of non-ACT drugs which is contrary to the current national guidelines for the treatment of uncomplicated malaria calls for urgent evaluation of treatment policy in the health facility.Keywords: Malaria, diagnosis, under-fives, treatment pattern, ACT