Wellington Oyibo

A current analysis of chemotherapy strategies for the treatment of human African trypanosomiasis

Abstract 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.

Prevalence of malaria in pregnant women in Lagos, South-West Nigeria.

Prevalence rates reported for malaria in pregnancy in Nigeria vary considerably. The accuracy of results of malaria diagnosis is dependent on training, experience, and motivation of the microscopist as well as the laboratory facility available. Results of training programmes on malaria microscopy have shown low levels of sensitivity and specificity of those involved in malaria diagnosis routinely and for research. This study was done to ascertain the true prevalence of malaria in pregnancy in Lagos, South-West Nigeria. A total of 1,084 pregnant women were recruited into this study. Blood smears stained with Giemsa were used for malaria diagnosis by light microscopy. Malaria infection during pregnancy presents mostly as asymptomatic infection. The prevalence of malaria in this population was 7.7% (95% confidence interval; 6.2-9.4%). Factors identified to increase the risk of malaria infection include young maternal age (< 20 years), and gravidity (primigravida). In conclusion, this study exposes the over-diagnosis of malaria in pregnancy and the need for training and retraining of laboratory staffs as well as establishing the malaria diagnosis quality assurance programme to ensure the accuracy of malaria microscopy results at all levels.

Strongyloides stercoralis and the immune response.

The immune system is a highly evolved network of cells and molecules that can distinguish between invading pathogens and the bodys 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.

Overdiagnosis and Overtreatment of Malaria in Children That Presented with Fever in Lagos, Nigeria

Background. Malaria diagnosis has been largely done clinically. The implication is the likely overdiagnosis of malaria when diagnosis is done soley on the basis of symptoms. Methods. Parasitological diagnosis was done among 1211, 0–12 years old febrile children that attended a Primary Health Centre in Lagos, Nigeria, who were diagnosed clinically and treated based on symptoms. Results. A total of 251 of 1,211 (20.7%) children less than 12 years old and 174 of the 1,027 of children 0–≤5 yrs (16.9%) were slide positive while 853 (83.1%) of 0–≤5 yrs that were slide negative were treated with Artemisinin based combination therapies (ACTs) in line with the Integrated Management of Childhood Infectioins (IMCI) guidelines and standard practice of the Clinic. Chills, diarrhoea, convulsions, headache, cough, respiratory distress, inactivity, loss of apetite, and vomiting occured significantly in the 0–≤5 and >5–12 years old malaria negative children. Conclusions. Overdiagnosis and overtreatment of malaria in this study was high. Therefore, malaria medicines should be prescribed on the basis of parasitological confirmation of all suspected malaria cases. The availability of quality-assured malaria rapid diagnostic tests (RDTs) is a useful tool to confirm malaria cases while the cause of the non-malaria fevers can be followed up and managed appropriately.

Factors associated with risk of malaria infection among pregnant women in Lagos, Nigeria

BackgroundPregnant women living in an area of stable malaria transmission such as Lagos, Nigeria, have been identified as being at an increased risk of the effects of malaria infection. In this area, most of the infections are asymptomatic which means they are overlooked and untreated much to the detriment of the mother and her foetus. The reality of scaled-up malaria interventions with long-lasting insecticide treated nets, vector control, artemisinin combination therapy (ACT) and intermittent preventive treatment of malaria pregnancy (IPTp) using sulphadoxine pyrimethamine (SP) is that it is also essential to determine the risk factors at play in these kinds of circumstances. This study was aimed at identifying the factors associated with risk of malaria infection in pregnant women in Lagos, Southwest Nigeria.MethodsDemographic information and malaria prevention practices of the pregnant women studied were captured using structured questionnaire. Microscopy was used to establish malaria infection, species identification and parasite density. Relative risk and multivariate logistic regression analysis were used to compare factors associated with malaria in pregnant women.ResultsMalaria microscopy details, demographic information and malaria prevention practices of the pregnant women were obtained using a structured questionnaire. The prevalence of malaria using peripheral blood from 1,084 pregnant women that participated in the study was 7.7%. Plasmodium falciparum (P. falciparum) was seen in 95.2% of the cases as either mixed infection with P. malariae (3.6%) or as a mono infection (91.6%). Malaria preventive practices associated with a significant reduction (P<0.05) in the malaria infection was the use of insecticide sprays (RR = 0.36, 95 C.I. 0.24-0.54), and the combined use of insecticide spray and insecticide-treated nets (ITN) (RR= 6.53, 95% C.I. 0.92-46.33). Sleeping under ITN alone (RR = 1.07, 95% C.I. 0.55-2.09) was not associated with significant reduction in malaria infection among the study participants with malaria parasitaemia. Young maternal age (<20years) (RR = 2.86, 95% C.I. 1.48 – 5.50), but not primigravidity (RR = 1.36, 95% C.I. 0.90-2.05), was associated with an increased risk of malaria infection during pregnancy. After a multivariate logistic regression, young maternal age (OR = 2.61, 95% C.I. 1.13 – 6.03) and the use of insecticide spray (OR = 0.38, 95% C.I. 0.24-0.63) were associated with an increase and a reduction in malaria infection, respectively.ConclusionMalaria prevalence was low among the pregnant women studied. Young maternal age and non-usage of insecticidal spray were the main factors associated with an increased risk of malaria infection among pregnant women in Lagos, Nigeria.

Identification and Characterization of Microsporidia from Fecal Samples of HIV-Positive Patients from Lagos, Nigeria

Background Microsporidia are obligate intracellular parasites that infect a broad range of vertebrates and invertebrates. They have been increasingly recognized as human pathogens in AIDS patients, mainly associated with a life-threatening chronic diarrhea and systemic disease. However, to date the global epidemiology of human microsporidiosis is poorly understood, and recent data suggest that the incidence of these pathogens is much higher than previously reported and may represent a neglected etiological agent of more common diseases indeed in immunocompetent individuals. To contribute to the knowledge of microsporidia molecular epidemiology in HIV-positive patients in Nigeria, the authors tested stool samples proceeding from patients with and without diarrhea. Methodology/Principal Findings Stool samples from 193 HIV-positive patients with and without diarrhea (67 and 126 respectively) from Lagos (Nigeria) were investigated for the presence of microsporidia and Cryptosporidium using Weber’s Chromotrope-based stain, Kinyoun stain, IFAT and PCR. The Weber stain showed 45 fecal samples (23.3%) with characteristic microsporidia spores, and a significant association of microsporidia with diarrhea was observed (O.R.  = 18.2; CI: 95%). A similar result was obtained using Kinyoun stain, showing 44 (31,8%) positive samples with structures morphologically compatible with Cryptosporidium sp, 14 (31.8%) of them with infection mixed with microsporidia. The characterization of microsporidia species by IFAT and PCR allowed identification of Enterocytozoon bieneusi, Encephalitozoon intestinalis and E. cuniculi in 5, 2 and 1 samples respectively. The partial sequencing of the ITS region of the rRNA genes showed that the three isolates of E.bieneusi studied are included in Group I, one of which bears the genotype B. Conclusions/Significance To our knowledge, this is the first report of microsporidia characterization in fecal samples from HIV-positive patients from Lagos, Nigeria. These results focus attention on the need to include microsporidial diagnosis in the management of HIV/AIDS infection in Nigeria, at the very least when other more common pathogens have not been detected.

Preliminary enquiry into the availability, price and quality of malaria rapid diagnostic tests in the private health sector of six malaria-endemic countries.

Objectives  This enquiry aimed to provide a snap‐shot of availability, price and quality of malaria rapid diagnostic tests (RDTs) in private health facilities at selected sites in six malaria‐endemic countries in Africa, South East Asia and South America.

Blood transfer devices for malaria rapid diagnostic tests: evaluation of accuracy, safety and ease of use

BackgroundMalaria rapid diagnostic tests (RDTs) are increasingly used by remote health personnel with minimal training in laboratory techniques. RDTs must, therefore, be as simple, safe and reliable as possible. Transfer of blood from the patient to the RDT is critical to safety and accuracy, and poses a significant challenge to many users. Blood transfer devices were evaluated for accuracy and precision of volume transferred, safety and ease of use, to identify the most appropriate devices for use with RDTs in routine clinical care.MethodsFive devices, a loop, straw-pipette, calibrated pipette, glass capillary tube, and a new inverted cup device, were evaluated in Nigeria, the Philippines and Uganda. The 227 participating health workers used each device to transfer blood from a simulated finger-prick site to filter paper. For each transfer, the number of attempts required to collect and deposit blood and any spilling of blood during transfer were recorded. Perceptions of ease of use and safety of each device were recorded for each participant. Blood volume transferred was calculated from the area of blood spots deposited on filter paper.ResultsThe overall mean volumes transferred by devices differed significantly from the target volume of 5 microliters (p < 0.001). The inverted cup (4.6 microliters) most closely approximated the target volume. The glass capillary was excluded from volume analysis as the estimation method used is not compatible with this device. The calibrated pipette accounted for the largest proportion of blood exposures (23/225, 10%); exposures ranged from 2% to 6% for the other four devices. The inverted cup was considered easiest to use in blood collection (206/226, 91%); the straw-pipette and calibrated pipette were rated lowest (143/225 [64%] and 135/225 [60%] respectively). Overall, the inverted cup was the most preferred device (72%, 163/227), followed by the loop (61%, 138/227).ConclusionsThe performance of blood transfer devices varied in this evaluation of accuracy, blood safety, ease of use, and user preference. The inverted cup design achieved the highest overall performance, while the loop also performed well. These findings have relevance for any point-of-care diagnostics that require blood sampling.

Comparative study of entero-parasitic infections among HIV sero-positive and sero-negative patients in Lagos, Nigeria.

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.

Molecular surveillance of drug-resistant Plasmodium falciparum in two distinct geographical areas of Nigeria

ZusammenfassungDie Entwicklung von therapie-resistenter Plasmodium falciparum-Malaria ist seit langem als Haupthindernis zur Bekämpfung von Mortalität und Morbidität erkannt. Wir haben daher die Verbreitung von Genveränderungen, die mit der Resistenz gegen Chloroquine und Pyrimethamin assoziiert sind, in P. falciparum-Isolaten aus zwei geographisch distinkten Gegenden in Nigeria untersucht. Mit Hilfe von RT-PCR und DNA-Sequenzierung wurde die Prävalenz dieser Mutationen bestimmt. Die Prävalenz der pfcrt T76-Mutation in den beiden Gegenden war 92.3 % gegen 86 % in Osogbo verglichen mit 93 % in Lafia (P = 0.4453). Sequenzanalyse des pfcrt Haplotyps (Aminosäuren 72–76) ergab CVIET als einzigen resistenten Haplotyp an beiden Orten. Die Häufigkeit von pfmdr1-Polymorphismen war höher in Lafia (39 %) als in Osogbo (35 %); die kombinierte Prävalenz in beiden Orten war 45.5 % (P = 0.6604). Die Prävalenz der pfdhfr-Triplemutante war hoch in beiden Gegenden: in Osogbo 84 % gegenüber 91 % in Lafia für I51, sowie 88 % gegen 87 % und 96 % gegen 96 % für die R59 and N108 Mutationen. Die kombinierte Prävalenz von pfcrt- und pfmdr1–Mutationen in Osogbo und Lafia war 44.2 % mit einem Risiko von 0.4164; die kombinierte Prävalenz aller Genveränderungen in pfcrt, pfmdr1 and pfdhfr war 40.4 % mit einem Risiko von 1.081. Diese Ergebnisse zeigen die weite Verbreitung der Resistenz gegen Chloroquin und Pyrimethamin in beiden untersuchten Regionen.SummaryDrug resistance against P. falciparum has been recognized as the crucial obstacle to curbing mortality and morbidity from malaria. We therefore determined the baseline distribution of pfcrt and pfmdr1 genes associated with resistance to chloroquine and pfdhfr gene associated with resistance to pyrimethamine in P. falciparum isolates collected from two geographically distinct areas of Nigeria. We use RT-PCR assays and sequencing to determine the prevalence of these mutations. The combined prevalence of pfcrt T76 mutation in the two sites was 92.3% with 86% from Osogbo compared to 93% from Lafia. Sequencing analysis of the (Pfcrt) K76T haplotype (amino acids 72–76) revealed CVIET as the only resistance haplotype present in the two areas. The frequency of pfmdr1 polymorphisms was higher in Lafia (39%) compared to that in Osogbo (35%) and the combined prevalence from the two sites was 45.5%. The prevalence of the pfdhfr triple mutant alleles was high in both locations. The Osogbo vs Lafia prevalence for pfdhfr mutations was 84% vs 91%, 88% vs 87% and 96% vs 96% for I51, R59 and N108, respectively. None of the samples from the two locations had the T108 mutation. The combined prevalence of pfcrt and pfmdr1 in Osogbo and Lafia was 44.2% with a risk ratio of 0.4164 while the combined prevalence of pfcrt,pfmdr1 and pfdhfr was 40.4% with a risk ratio of 1.081. These results strongly suggest the widespread distribution of CQ and pyrimethamine resistance without any marked distinction between the two locations.