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1.
Bull World Health Organ ; 98(12): 859-868, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33293746

RESUMO

Objective: To determine the regional- and district-level newborn prevalence of sickle cell trait and disease, and the prevalence of haemoglobin variants and genetic modifiers of sickle cell disease, in the nine regions of north-western United Republic of Tanzania. Methods: We repurposed dried blood spot samples from children (aged 0-24 months) born to mothers living with human immunodeficiency virus (HIV), collected as part of the HIV Early Infant Diagnosis programme, for sickle cell diagnosis. We performed isoelectric focusing to determine whether samples had normal haemoglobin, sickle cell trait, sickle cell disease or a rare haemoglobin variant. We shipped samples diagnosed as disease or variant to Cincinnati Children's Hospital in the United States of America for deoxyribonucleic-acid-based analyses to determine the prevalence of α-thalassaemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency or fetal haemoglobin genetic modifiers. Findings: We analysed a total of 17 200 specimens during February 2017-May 2018. We observed a prevalence of sickle cell trait and disease of 20.3% (3492/17 200) and 1.2% (210/17 200), respectively. District-level trait varied from 8.6% (5/58) to 28.1% (77/274). Among confirmed sickle cell disease specimens, we noted 42.7% (61/143) had 1-gene deletion and 14.7% (21/143) had 2-gene deletion α-thalassaemia trait. We documented G6PD A- deficiency in 19.2% (14/73) of males. Conclusion: Our calculated prevalence is twice as high as previously reported and reinforces the need for enhanced sickle cell diagnostic services. Our district-level data will inform public health policy, allowing screening and disease-modifying hydroxyurea therapy to be focused on high-prevalence areas, until universal newborn screening is available.

2.
Mol Ecol ; 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33107096

RESUMO

High-throughput Plasmodium genomic data is increasingly useful in assessing prevalence of clinically important mutations and malaria transmission patterns. Understanding parasite diversity is important for identification of specific human or parasite populations that can be targeted by control programmes, and to monitor the spread of mutations associated with drug resistance. An up-to-date understanding of regional parasite population dynamics is also critical to monitor the impact of control efforts. However, this data is largely absent from high-burden nations in Africa, and to date, no such analysis has been conducted for malaria parasites in Tanzania countrywide. To this end, over 1,000 P. falciparum clinical isolates were collected in 2017 from 13 sites in seven administrative regions across Tanzania, and parasites were genotyped at 1,800 variable positions genome-wide using molecular inversion probes. Population structure was detectable among Tanzanian P. falciparum parasites, approximately separating parasites from the northern and southern districts and identifying genetically admixed populations in the north. Isolates from nearby districts were more likely to be genetically related compared to parasites sampled from more distant districts. Known drug resistance mutations were seen at increased frequency in northern districts (including two infections carrying pfk13-R561H), and additional variants with undetermined significance for antimalarial resistance also varied by geography. Malaria Indicator Survey (2017) data corresponded with genetic findings, including average region-level complexity-of-infection and malaria prevalence estimates. The parasite populations identified here provide important information on extant spatial patterns of genetic diversity of Tanzanian parasites, to which future surveys of genetic relatedness can be compared.

3.
Malar J ; 18(1): 88, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30898164

RESUMO

BACKGROUND: The World Health Organization recommends regular therapeutic efficacy studies (TES) to monitor the performance of first and second-line anti-malarials. In 2016, efficacy and safety of artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria were assessed through a TES conducted between April and October 2016 at four sentinel sites of Kibaha, Mkuzi, Mlimba, and Ujiji in Tanzania. The study also assessed molecular markers of artemisinin and lumefantrine (partner drug) resistance. METHODS: Eligible patients were enrolled at the four sites, treated with standard doses of AL, and monitored for 28 days with clinical and laboratory assessments. The main outcomes were PCR corrected cure rates, day 3 positivity rates, safety of AL, and prevalence of single nucleotide polymorphisms in Plasmodium falciparum kelch 13 (Pfk13) (codon positions: 440-600) and P. falciparum multi-drug resistance 1 (Pfmdr1) genes (codons: N86Y, Y184F and D1246Y), markers of artemisinin and lumefantrine resistance, respectively. RESULTS: Of 344 patients enrolled, three withdrew, six were lost to follow-up; and results were analysed for 335 (97.4%) patients. Two patients had treatment failure (one early treatment failure and one recrudescent infection) after PCR correction, yielding an adequate clinical and parasitological response of > 98%. Day 3 positivity rates ranged from 0 to 5.7%. Common adverse events included cough, abdominal pain, vomiting, and diarrhoea. Two patients had serious adverse events; one died after the first dose of AL and another required hospitalization after the second dose of AL (on day 0) but recovered completely. Of 344 samples collected at enrolment (day 0), 92.7% and 100% were successfully sequenced for Pfk13 and Pfmdr1 genes, respectively. Six (1.9%) had non-synonymous mutations in Pfk13, none of which had been previously associated with artemisinin resistance. For Pfmdr1, the NFD haplotype (codons N86, 184F and D1246) was detected in 134 (39.0%) samples; ranging from 33.0% in Mlimba to 45.5% at Mkuzi. The difference among the four sites was not significant (p = 0.578). All samples had a single copy of the Pfmdr1 gene. CONCLUSION: The study indicated high efficacy of AL and the safety profile was consistent with previous reports. There were no known artemisinin-resistance Pfk13 mutations, but there was a high prevalence of a Pfmdr1 haplotype associated with reduced sensitivity to lumefantrine (but no reduced efficacy was observed in the subjects). Continued TES and monitoring of markers of resistance to artemisinin and partner drugs is critical for early detection of resistant parasites and to inform evidence-based malaria treatment policies. Trial Registration ClinicalTrials.gov NCT03387631.


Assuntos
Antimaláricos/efeitos adversos , Combinação Arteméter e Lumefantrina/efeitos adversos , Resistência a Medicamentos/genética , Malária/prevenção & controle , Polimorfismo de Nucleotídeo Único/efeitos dos fármacos , Proteínas de Protozoários/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Proteínas de Protozoários/metabolismo , Tanzânia
4.
Malar J ; 17(1): 369, 2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30333022

RESUMO

BACKGROUND: Artemisinin-based combination therapy (ACT) is the first-line anti-malarial treatment of uncomplicated malaria in most malaria endemic countries, including Tanzania. Unfortunately, there have been reports of artemisinin resistance and ACT failure from South East Asia highlighting the need to monitor therapeutic efficacy of ACT in these countries as recommended by World Health Organization. METHODS: Open-label single arm studies in mainland Tanzania were conducted in nine sentinel sites in 2011, 2012 and 2015 to assess the efficacy and safety of artemether/lumefantrine (AL) and artesunate/amodiaquine (ASAQ) using 28 days follow-up and dihydroartemisinin/piperaquine (DHAPQ) using 42 days follow-up. Mutations in the propeller domain of the Plasmodium falciparum kelch 13 (k13) gene and amplification of the P. falciparum plasmepsin 2 (pm2) gene, associated with artemisinin and piperaquine (PQ) resistance, were also investigated. RESULTS: Of the 428 patients enrolled, 328 patients provided study endpoint. For AL, the PCR corrected per-protocol analysis showed adequate clinical and parasitological response (ACPR) of 90.3% (n = 28; 95% CI 74.2-98.0) in Kyela 2012, 95.7% (n = 22; 95% CI 78.1-99.0) in Chamwino, 100% in Muheza (n = 29; 95% CI 88.1-100), 100% in Nagaga (n = 39; 95% CI 91.0-100) and Kyela 2015 (n = 60; 95% CI 94.0-100). For ASAQ, PCR corrected ACPR of 98% (n = 49; 95% CI 89.4-99.9) and 100% (n = 25; 95% CI 86.3-100) were observed in 2011 in Ujiji and Kibaha, respectively. For DHAPQ, the ACPR was 100% (n = 71; 95% CI 94.9-100). Of the 235 samples with genetic interpretable results, only 7 (3%) had non-synonymous k13 mutations. None of these are candidate or validated markers of artemisinin resistance and all patients carrying these alleles cleared the parasites on day 3. Of the DHAPQ group, 10% (3/29) of the samples with interpretable results had pm2 multiple copies and none of them was associated with treatment failure. CONCLUSION: All the tested ACT in mainland Tanzania were highly efficacious and none of validated k13 mutants associated with artemisinin resistance was observed. However, three isolates with multiple copy numbers of pm2 gene associated with PQ resistance among the limited samples tested successfully calls for further investigation. Trial registration Number ACTRN12615000159550. Registered 18th February 2015, https://www.anzctr.org.au/trial/MyTrial.aspx.


Assuntos
Amodiaquina/uso terapêutico , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/prevenção & controle , Quinolinas/uso terapêutico , Adolescente , Amodiaquina/efeitos adversos , Antimaláricos/efeitos adversos , Combinação Arteméter e Lumefantrina/efeitos adversos , Artemisininas/efeitos adversos , Criança , Pré-Escolar , Combinação de Medicamentos , Feminino , Humanos , Lactente , Masculino , Plasmodium falciparum/efeitos dos fármacos , Estudos Prospectivos , Quinolinas/efeitos adversos , Tanzânia
5.
Arch Public Health ; 76: 39, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30065835

RESUMO

Background: Malaria continued to be the major public health concern in sub-Sahara Africa, thus for better planning of control activities, periodic surveillance of both clinical and asymptomatic cases remains important. However, the usability of routinely collected malaria data in Kenyan hospitals as a predictor of the asymptomatic malaria infection in the community amidst rapid infection resurgence or reduction in different areas of disease endemicities remains widely unstudied. This study was therefore aimed to evaluate the utility of passive surveillance of malaria in health facilities as a proxy of infection transmission of the surrounding community in different transmission intensities. Methods: Prospective multiple cross-sectional surveys were done in three villages in western Kenya. Monthly asymptomatic malaria positivity among school children, number of outpatient (OPD) confirmed malaria cases and abundancy of indoor resting malaria vectors were surveyed from June 2015 to August 2016. Community surveys on antimalarial drug use among adults and children were also done. Detection of malaria parasitaemia was done using thick and thin Giemsa stained blood slide microscopy for both clinical and school participants. A questionnaire was used to collect information on self-use of antimalarial drugs from randomly selected households. Results: The overall OPD blood slide positivity from all study sites was 26.6% (95%CI 26.2-27.0) and highest being among the 5-14 years (41.2% (95% CI 40.1-42.3). Asymptomatic malaria positivity among the school children were 6.4% (95%CI 5.3-7.5) and 38.3% (95%CI 36.1-40.5) in low and high transmission settings respectively. A strong correlation between overall monthly OPD positivity and the school age children positivity was evident at Marani (low transmission) (rho = 0.78, p = 0.001) and at Iguhu (Moderate transmission) (rho = 0.61, p = 0.02). The high transmission setting (Kombewa) showed no significant correlation (rho = - 0.039, p = 0.89). Conclusion: Hospital malaria data from low and moderate malaria transmission predicted the infection transmission dynamics of the surrounding community. In endemic sites, hospital based passive surveillance didn't predict the asymptomatic infection dynamics in the respective community.

6.
PLoS One ; 13(8): e0202031, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30092043

RESUMO

BACKGROUND: Passive surveillance of malaria in health facilities remains vital for implementation of control and elimination programs. It is therefore essential understanding current age profile of clinical malaria morbidity, mortality and presentations in areas with variant infection susceptibility. This study aimed at understanding the current malaria morbidity and mortality in Western Kenya. METHODS: Surveillance of clinical and asymptomatic parasitological positivity rates of all malaria suspected patients and school children were respectively determined from June 2015 to August 2016. From 2014 to 2016, register books in hospitals were referred and the confirmed malaria cases in conjunction with total number of monthly outpatient visits (OPD) counted. All registered malaria admissions were counted together with other causes of admissions. Moreover, outcome of malaria admissions in terms of discharge or death was recorded using inpatient charts within the same time frame. Prospective surveillance of severe malaria collected information on clinical features of the disease. Giemsa stained blood slides confirmed existence of malaria parasitemia. Chi-square and analysis of variance tests were used, respectively, to compute proportions and means; then a comparison was made between different age groups, periods, and study areas. RESULTS: During the survey of asymptomatic infections among school children, overall blood slide positivity ranged from 6.4% at the epidemic prone site to 38.3% at the hyperendemic site. During the clinical malaria survey, school age children (5-14) presented with overall the highest (45%) blood slide positivity rate among those suspected to have the infection at the epidemic prone study site. The survey of all malaria confirmed and registered cases at OPD found 17% to 27% of all consultations among <5 children and 9.9% to 20.7% of all OPD visits among the ≥5 patients were due to malaria. Moreover, survey of all registered causes of admission in hospitals found 47% of admissions were due to malaria. The disease was a major cause of admission in epidemic prone setting where 63.4% of the <5 children and 62.8% of the ≥5 patients were admitted due to malaria (p>0.05) and 40% of all malaria admissions were school age children. Malaria related death rate was highest among <5 years at the hyperendemic site, that is 60.9 death per 1000 malaria <5 admissions. Conversely, the epidemic prone setting experienced highest malaria related death among ≥15 years (18.6 death per 1000 admissions) than the < 15 years (5.7 death per 1000 admissions of the <15 years) (p< 0.001). Surveillance of severe form of the disease found that hyperpyrexia, hyperparastemia, prostration and convulsions as common presentations of severe disease. CONCLUSION: Malaria is still the major cause of hospital consultations in Western Kenya with an alarming number of severe forms of the disease among the school aged children at the epidemic prone setting. Mortalities were higher among <5 children years in high infection transmission setting and among ≥15 years in low and moderate transmission settings. Surveillance of asymptomatic and symptomatic malaria along with evaluation of current interventions in different age groups should be implemented in Kenya.


Assuntos
Malária/mortalidade , Malária/transmissão , Adolescente , Adulto , Antimaláricos/uso terapêutico , Criança , Pré-Escolar , Controle de Doenças Transmissíveis , Feminino , Hospitalização , Humanos , Quênia/epidemiologia , Malária/epidemiologia , Masculino , Pacientes Ambulatoriais , Parasitemia/tratamento farmacológico , Alta do Paciente , Vigilância da População , Prevalência , Estudos Prospectivos , Saúde Pública , Estações do Ano , Adulto Jovem
7.
BMC Pregnancy Childbirth ; 18(1): 16, 2018 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-29310609

RESUMO

BACKGROUND: Self-medication is a universal challenge that requires attention because of the potential threat not only to the pregnant women but also to unborn child. Data on self-medication practice and predictors among pregnant women is lacking in Tanzania. Information on the effects of this practice to the pregnant woman and the foetus globally is also scanty. METHODS: This was a cross sectional study which was conducted using face to face interview with 372 pregnant women at Makongoro health centre. Semi-structured questionnaires were used. Data were analysed using STATA 13 (Statistical Corporation, College Station, Texas, US). RESULTS: A total of 372 pregnant women participated in the study. The prevalence of self-medication among pregnant women was 172 (46.24%). There was a significant statistical association between self-medication and occupation (P value =0.01), gestation age (P < 0.01) and education (P < 0.01). Age, marital status and gravidity were not associated with self-medication (P = 0.809, P = 0.243 and P = 0.922) respectively. When bivariate logistic regression was performed, occupation and education were the only determining factors for self-medication. Pregnant women who were unemployed, doing business and house wife were most likely to practice self-medication than employed pregnant women (P = 0.03; OR = 2.33; 95% CI, 1.06-5.31, P = 0.01; OR = 2.31; CI 1.21-4.41, P = <0.01, OR = 2.73, 95% CI 0.52-2.43) respectively. Pregnant women with no formal education, incomplete primary education, primary education and secondary education were most likely to practice self-medication than pregnant women with college or university education (P < 0.01, OR = 6.37 95% CI 2.37-19.03, P < 0.01, OR = 6.58, 95% CI 2.36-18.25, P < 0.01, OR = 3.78, 95% CI 1.89-7.56, P < 0.01, OR = 2.59 95% CI = 1.30-5.17). The leading illness/symptoms which led to self-medication among pregnant women attending clinic were malaria 56 (32.56%, morning sickness 44 (25.55%) and headache 33(19.19%). Drugs commonly used in self-medication among pregnant women were ant malarial 42 (24.42%), antiemetics 59 (34.30%) and analgesics 33 (19.19%). CONCLUSION: Prevalence of self-medication among pregnant women is high in Tanzania. This is a threat to the safety of the developing foetus and the pregnant woman. Therefore there is a need of interventions to minimize the practice among pregnant women.


Assuntos
Analgésicos/uso terapêutico , Antieméticos/uso terapêutico , Antimaláricos/uso terapêutico , Automedicação/estatística & dados numéricos , Adolescente , Adulto , Comércio , Estudos Transversais , Escolaridade , Feminino , Idade Gestacional , Cefaleia/tratamento farmacológico , Serviço de Limpeza , Humanos , Malária/tratamento farmacológico , Pessoa de Meia-Idade , Êmese Gravídica/tratamento farmacológico , Gravidez , Inquéritos e Questionários , Tanzânia , Desemprego , Adulto Jovem
8.
Pediatr Blood Cancer ; 65(1)2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28766840

RESUMO

BACKGROUND: Worldwide, hemoglobinopathies affect millions of children. Identification of hemoglobin disorders in most sub-Saharan African countries is delayed until clinical signs of the disease are present. Limited studies have been conducted to understand their prevalence and clinical presentation among newborns in resource-limited settings. METHODOLOGY: This was a prospective cohort study. Newborns (aged 0-7 days) at two hospitals in Northwestern Tanzania were enrolled and followed prospectively for 6 months. Clinical and laboratory information were collected at baseline. Participants were screened for hemoglobinopathies using high-performance liquid chromatography. Clinical and laboratory follow-up was performed at 3 and 6 months for those with hemoglobinopathies as well as a comparison group of participants without hemoglobinopathies. RESULTS: A total of 919 newborns were enrolled. Among these, 1.4% (13/919) had sickle cell anemia or Hb S/ß0 -thalassemia (Hb FS), and 19.7% (181/919) had sickle cell trait or Hb S/ß+ thalassemia (Hb FAS). Furthermore, 0.2% (two of 919) had ß+ -thalassemia. Red cell indices compared between Hb FS, Hb FAS, and Hb FA were similar at baseline, but hemoglobin was lower and red cell distribution width was higher in children with Hb FS at 3- and 6-month follow-up. Febrile episodes were more common for children with Hb FS at 3- and 6-month follow-up. CONCLUSION: The prevalence of sickle cell disease among neonates born in Northwestern Tanzania is one of the highest in the world. Newborn screening is needed early in life to identify neonates with hemoglobinopathies so that clinical management may commence and morbidity and mortality related to hemoglobinopathies be reduced.


Assuntos
Anemia Falciforme/epidemiologia , Doenças do Recém-Nascido/epidemiologia , Adulto , Anemia Falciforme/sangue , Feminino , Seguimentos , Humanos , Recém-Nascido , Doenças do Recém-Nascido/sangue , Masculino , Prevalência , Estudos Prospectivos , Tanzânia/epidemiologia
9.
Ann Hematol ; 97(2): 239-246, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29147848

RESUMO

Both anemia and sickle cell disease (SCD) are highly prevalent across sub-Saharan Africa, and limited resources exist to diagnose these conditions quickly and accurately. The development of simple, inexpensive, and accurate point-of-care (POC) assays represents an important advance for global hematology, one that could facilitate timely and life-saving medical interventions. In this prospective study, Robust Assays for Point-of-care Identification of Disease (RAPID), we simultaneously evaluated a POC immunoassay (Sickle SCAN™) to diagnose SCD and a first-generation POC color-based assay to detect anemia. Performed at Bugando Medical Center in Mwanza, Tanzania, RAPID tested 752 participants (age 1 day to 20 years) in four busy clinical locations. With minimally trained medical staff, the SCD POC assay diagnosed SCD with 98.1% sensitivity and 91.1% specificity. The hemoglobin POC assay had 83.2% sensitivity and 74.5% specificity for detection of severe anemia (Hb ≤ 7 g/dL). Interobserver agreement was excellent for both POC assays (r = 0.95-0.96). Results for the hemoglobin POC assay have informed the second-generation assay design to be more suitable for low-resource settings. RAPID provides practical feasibility data regarding two novel POC assays for the diagnosis of anemia and SCD in real-world field evaluations and documents the utility and potential impact of these POC assays for sub-Saharan Africa.


Assuntos
Anemia Falciforme/diagnóstico , Anemia/diagnóstico , Colorimetria/métodos , Hemoglobinas/metabolismo , Testes Imediatos , Adolescente , Anemia/sangue , Anemia Falciforme/sangue , Criança , Pré-Escolar , Colorimetria/economia , Feminino , Humanos , Imunoensaio , Lactente , Recém-Nascido , Masculino , Variações Dependentes do Observador , Estudos Prospectivos , Sensibilidade e Especificidade , Tanzânia , Adulto Jovem
10.
Malar J ; 16(1): 498, 2017 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-29284476

RESUMO

BACKGROUND: In sub-Saharan Africa, malaria interventions over the last decades have been successful in reducing both mortality and morbidity. In western Kenya however some areas experience contrasting outcomes of the ongoing interventions while the causes for this observation remains not yet clearly known. METHODS: The WHO insecticide (deltamethrin) susceptibility test of the common malaria vectors was studied. Multiple surveys on household use and hospital prescriptions of antimalarial drugs from 2003 to 2015 were done. Along with this, cross sectional surveys on their availability in the local drug dispensing outlets were also done in 2015. Monthly precipitations and air temperature data was collected along with systematic review on abundance and composition of common malaria vectors in the study area before and during interventions. The above factors were used to explain the possible causes of contrasting outcome of malaria interventions between the three study sites. RESULTS: Areas with malaria resurgence or sustained high transmission (Kombewa and Marani) showed higher composition of Anopheles funestus sensu lato (s.l.) than the previously abundant Anopheles gambiae sensu stricto (s.s.) and the later had higher composition to an area with a sustained infection decline (Iguhu). Anopheles gambiae s.l. from Kombewa showed highest resistance (50% mortality) upon exposure to WHO deltamethrin discriminating dosage of 0.75% while those from Marani and Iguhu had reduced resistance status (both had a mean mortality of 91%). Sampled An. funestus s.l. from Marani were also highly resistant to deltamethrin as 57% of the exposed vectors survived. An increasing of mean air temperature by 2 °C was noted for Marani and Iguhu from 2013 to 2015 and was accompanied by an increased rainfall at Marani. Community drug use and availability in selling outlets along with prescription in hospitals were not linked to the struggling control of the disease. CONCLUSIONS: The malaria vector species composition shift, insecticide resistance and climatic warming were the likely cause of the contrasting outcome of malaria intervention in western Kenya. Surveillance of malaria parasite and vector dynamics along with insecticide resistance and vector biting behaviour monitoring are highly recommended in these areas.


Assuntos
Antimaláricos/uso terapêutico , Malária/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Animais , Antimaláricos/administração & dosagem , Mordeduras e Picadas/parasitologia , Mudança Climática , Estudos Transversais , Vetores de Doenças , Intervenção Médica Precoce/estatística & dados numéricos , Geografia , Humanos , Resistência a Inseticidas , Mosquiteiros Tratados com Inseticida/estatística & dados numéricos , Inseticidas/administração & dosagem , Quênia/epidemiologia , Malária/epidemiologia , Malária/parasitologia , Controle de Mosquitos/métodos , Mosquitos Vetores/efeitos dos fármacos , Nitrilos/administração & dosagem , Densidade Demográfica , Piretrinas/administração & dosagem
11.
BMC Res Notes ; 10(1): 197, 2017 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-28595630

RESUMO

BACKGROUND: Highly Active Antiretroviral therapy (HAART) reverses the effect of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) by durably suppressing viral replication. This allows CD4 gain to levels that are adequate enough to restore the body's capability to fight against opportunistic infections (OIs). Patients with poor immune recovery have been shown to have higher risk of developing both AIDS and non AIDS related clinical events. This study aimed at assessing the proportions and risk factors of poor immune recovery in adult HIV-infected patients on 48 months of HAART attending care and treatment center (CTC) in northwestern Tanzania. METHODS: A retrospective analysis of adult HIV patients' data attending CTC at Sekou Toure hospital and who initiated HAART between February 2004 and January 2008 was done. Poor immune recovery was defined as a CD4 count less than 350 cells/µl on follow up as used in other studies. RESULTS: A total of 734 patients were included in the study. In this study 50.25% of patients attending CTC at Sekou Toure hospital were found to have poor immune recovery. The risk of developing inadequate immune recovery was independently associated with male gender, age older than 50 years, low baseline CD4 counts, and advanced World Health Organization (WHO) clinical stage. CONCLUSIONS: Poor immune recovery is prevalent among adult HIV patients attending CTC at Sekou Toure hospital in Northwestern part of Tanzania and opportunistic infections are common in this sub group of patients. Clinicians in resource limited countries need to identify these patients timely and plan them for targeted viral assessment and close clinical follow up to improve their long term clinical outcome.


Assuntos
Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Síndrome de Imunodeficiência Adquirida/imunologia , Síndrome de Imunodeficiência Adquirida/virologia , Adulto , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , HIV-1/imunologia , HIV-1/fisiologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Tanzânia/epidemiologia , Adulto Jovem
12.
BMC Health Serv Res ; 17(1): 70, 2017 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-28114988

RESUMO

BACKGROUND: Roll-out and implementation of antiretroviral therapy (ART) necessitated many countries in Sub-Saharan Africa to strengthen their national health laboratory systems (NHLSs) to provide high quality HIV diagnostic and supportive services. This study was conducted to assess the performance of health laboratories in provision of HIV diagnostic and supportive services in eight districts (from four regions of Iringa, Mtwara, Tabora and Tanga), after nine years of implementation of HIV/AIDS care and treatment plan in Tanzania. METHODS: In this cross-sectional study, checklists and observations were utilized to collect information from health facilities (HFs) with care and treatment centres (CTCs) for HIV/AIDS patients; on availability of laboratories, CTCs, laboratory personnel, equipment and reagents. A checklist was also used to collect information on implementation of quality assurance (QA) systems at all levels of the NHLS in the study areas. RESULTS: The four regions had 354 HFs (13 hospitals, 41 Health Centres (HCs) and 300 dispensaries); whereby all hospitals had laboratories and 11 had CTCs while 97.5 and 61.0% of HCs had both laboratories and CTCs, respectively. Of the dispensaries, 36.0 and 15.0% had laboratories and CTCs (mainly in urban areas). Thirty nine HFs (12 hospitals, 21 HCs and six dispensaries) were assessed and 56.4% were located in urban areas. The assessed HFs had 199 laboratory staff of different cadres (laboratory assistants = 35.7%; technicians =32.7%; attendants = 22.6%; and others = 9.1%); with >61% of the staff and 72.3% of the technicians working in urban areas. All laboratories were using rapid diagnostic tests for HIV testing. Over 74% of the laboratories were performing internal quality control and 51.4% were participating in external QA programmes. Regional and district laboratories had all key equipment and harmonization was maintained for Fluorescence-Activated Cell Sorting (FACS) machines. Most of the biochemical (58.0%) and haematological analysers (74.1%) were available in urban areas. Although >81% of the equipment were functional with no mechanical faulty, 62.6% had not been serviced in the past three years. CONCLUSION: Diagnostic and supportive services for HIV were available in most of the HCs and hospitals while few dispensaries were providing the services. Due to limitations such as shortage of staff, serving of equipment and participation in QA programmes, the NHLS should be strengthened to ensure adequate human resource, implementation of QA and sustainable preventive maintenance services of equipment.


Assuntos
Técnicas de Laboratório Clínico/normas , Controle de Doenças Transmissíveis/normas , Serviços de Diagnóstico/normas , Infecções por HIV/diagnóstico , Laboratórios/normas , Garantia da Qualidade dos Cuidados de Saúde/normas , Lista de Checagem , Controle de Doenças Transmissíveis/organização & administração , Estudos Transversais , Serviços de Diagnóstico/provisão & distribução , Humanos , Laboratórios/provisão & distribução , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Tanzânia
13.
Hematology ; 21(4): 248-256, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26868490

RESUMO

OBJECTIVES: Tanzania has the third highest birth rate of sickle cell anaemia (SCA) in Africa, but few studies describe severity of complications or available treatments, especially in Northwest Tanzania around Lake Victoria where the sickle gene is most prevalent. This is a report of the spectrum of clinical disease and range of interventions available at Bugando Medical Centre (Bugando) in Northwest Tanzania in Africa. METHODS: A cross-sectional study was carried out in Bugando between 1 August 2012 and 30 September 2012. Children (<15 years old) with SCA attending Bugando were sequentially enrolled. A trained research assistant completed a Swahili questionnaire with the parent or guardian of each participant concerning demographic information, clinical features of disease, and treatments received. RESULTS: Among the 124 participants enrolled, the median age was 6 years (interquartile range [IQR] 4-8.5), and only 13 (10.5%) were < 3 years old. Almost all participants (97.6%) had a prior history of a vaso-occlusive episode, 83 (66.9%) had prior acute chest syndrome, and 21 (16.9%) had prior stroke. In the preceding 12 months, 120 (96.8%) had been hospitalized, and a vaso-occlusive episode was the most common reason for hospitalization (35.5%). Prescriptions for folic acid (92.7%) and malaria prophylaxis (84.7%) were common, but only one had received a pneumococcal vaccine, and none had received hydroxyurea or prophylactic penicillin. CONCLUSION: Children with SCA receiving care in Tanzania are diagnosed late, hospitalized frequently, and have severe complications. Opportunities exist to improve care through wider access to screening and diagnosis as well as better coordination of comprehensive care.


Assuntos
Síndrome Torácica Aguda , Ácido Fólico/administração & dosagem , Hospitalização , Acidente Vascular Cerebral , Doenças Vasculares , Síndrome Torácica Aguda/complicações , Síndrome Torácica Aguda/epidemiologia , Síndrome Torácica Aguda/terapia , Criança , Pré-Escolar , Feminino , Humanos , Malária/complicações , Malária/epidemiologia , Malária/prevenção & controle , Masculino , Vacinas Pneumocócicas/administração & dosagem , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/terapia , Tanzânia/epidemiologia , Doenças Vasculares/epidemiologia , Doenças Vasculares/etiologia , Doenças Vasculares/terapia
14.
BMC Hematol ; 15: 13, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26464799

RESUMO

BACKGROUND: Anaemia is a major public health problem in developing countries, contributing significantly to morbidity and mortality amongst children under-five years of age. About 43 % of under-fives are anaemic worldwide, and two-thirds reside in sub-Saharan Africa. Even where blood transfusion is available for treatment there is still a significant case fatality rate ranging between 6 and 18 %. This study aimed to determine the prevalence and morphological types of anaemia, as well as factors associated with severe anaemia in under-five children admitted at Bugando Medical Centre (BMC). METHODS: This was a hospital-based, cross-sectional study conducted between November 2012 and February 2013. Selected laboratory investigations were done on children admitted to BMC. Anaemia was defined using WHO criteria. RESULTS: A total of 448 under-five children were recruited into the study. The overall prevalence of anaemia was 77.2 % (346/448) with mild, moderate and severe anaemia being 16.5, 33 and 27.7 % respectively. Microcytic hypochromic anaemia was detected in 37.5 % of the children with anaemia. Of 239 children with moderate and severe anaemia, 22.6 % (54/239) had iron deficiency anaemia based on serum ferritin level less than12 µg/ml. The factors associated with severe anaemia included unemployment of the parent, malaria parasitaemia and presence of sickle haemoglobin. CONCLUSION: The prevalence of anaemia among under-five children admitted at BMC was high. Iron deficiency anaemia was the most common type. Factors associated with severe anaemia were unemployment among caretakers, malaria parasitaemia and presence of sickle haemoglobin.

15.
Malar J ; 14: 264, 2015 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-26152336

RESUMO

BACKGROUND: Plasmodium falciparum resistance to anti-malarials is a major drawback in effective malaria control and elimination globally. Artemisinin-combination therapy (ACT) is currently the key first-line treatment for uncomplicated falciparum malaria. Plasmodium falciparum genetic signatures at pfmdr-1, pfcrt, and pfubp-1 loci are known to modulate in vivo and in vitro parasite response to ACT. The objective of this study was to assess the distribution of these resistance gene markers in isolates collected from different malaria transmission intensity in Ethiopia and Tanzania. METHODS: Plasmodium falciparum clinical isolates were collected from different regions of Ethiopia and Tanzania. Genetic polymorphisms in the genes pfcrt, pfmdr-1 and pfubp-1 were analysed by PCR and sequencing. Frequencies of the different alleles in the three genes were compared within and between regions, and between the two countries. RESULTS: The majority of the isolates from Ethiopia were mutant for the pfcrt 76 and wild-type for pfmdr-1 86. In contrast, the majority of the Tanzanian samples were wild-type for both pfcrt and pfmdr-1 loci. Analysis of a variable linker region in pfmdr-1 showed substantial variation in isolates from Tanzania as compared to Ethiopian isolates that had minimal variation. Direct sequencing of the pfubp-1 region showed that 92.8% (26/28) of the Ethiopian isolates had identical genome sequence with the wild type reference P. falciparum strain 3D7. Of 42 isolates from Tanzania, only 13 (30.9%) had identical genome sequences with 3D7. In the Tanzanian samples, 10 variant haplotypes were identified. CONCLUSION: The majority of Ethiopian isolates carried the main marker for chloroquine (CQ) resistance, while the majority of the samples from Tanzania carried markers for CQ susceptibility. Polymorphic genes showed substantially more variation in Tanzanian isolates. The low variability in the polymorphic region of pfmdr-1 in Ethiopia may be a consequence of low transmission intensity as compared to high transmission intensity and large variations in Tanzania.


Assuntos
Resistência a Medicamentos , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/genética , Polimorfismo Genético , Proteínas de Protozoários/genética , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Etiópia , Genótipo , Humanos , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/metabolismo , Proteínas de Protozoários/metabolismo , Tanzânia
16.
BMC Health Serv Res ; 15: 248, 2015 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-26113250

RESUMO

BACKGROUND: Strong health laboratory systems and networks capable of providing high quality services are critical components of the health system and play a key role in routine diagnosis, care, treatment and disease surveillance. This study aimed to assess the readiness of the national health laboratory system (NHLS) and its capacity to support care and treatment of HIV/AIDS in Tanzania. METHODS: A documentary review was performed to assess the structure of the health system with reference to the status and capacity of the NHLS to support HIV diagnosis. Key informant interviews were also held with laboratory staff in all levels of the health care delivery system in four regions with different levels of HIV prevalence. Information sought included availability and utilization of laboratory guidelines, quality and the capacity of laboratories for diagnosis of HIV. RESULTS: The findings indicate that a well-established NHLS was in place. However, the coordination of HIV laboratory services was found to be weak. Forty six respondents were interviewed. In most laboratories, guidelines for HIV diagnosis were available but health care providers were not aware of their availability. Utilization of the guidelines for HIV diagnosis was higher at national level than at the lower levels. The low level of awareness and utilization of guidelines was associated with inadequate training and supervision. There was a shortage of human resource, mostly affecting the primary health care level of the system and this was associated with inequity in employment and training opportunities. Laboratories in public health facilities were better staffed and had more qualified personnel than private-owned laboratories. CONCLUSION: Tanzania has a well established national health laboratory network sufficient to support HIV care and treatment services. However, laboratories at the primary health care level are constrained by inadequate resources and operate within a limited capacity. Improving the laboratory capacity in terms of number of qualified personnel, staff training on the national guidelines, laboratory diagnostic tools and coordination should be given a higher priority.


Assuntos
Serviços de Laboratório Clínico/normas , Infecções por HIV/tratamento farmacológico , Doenças Transmissíveis , Assistência à Saúde , Feminino , Pessoal de Saúde , Humanos , Entrevistas como Assunto , Masculino , Pesquisa Qualitativa , Inquéritos e Questionários , Tanzânia
17.
Ital J Pediatr ; 41: 44, 2015 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-26084628

RESUMO

BACKGROUND: Infections are common complications occurring in malnourished childrenas a result of impaired immunity. Urinary tract infections (UTI) have been found to be the commonest cause of fever in normal children in developing countries. However, data regarding UTI among malnourished children is limited because in most of time severe and moderately malnourished children are afebrile despite significant bacteriuria. METHODS: A total of 402 malnourished underfives were enrolled. Demographic and other clinical characteristics were collected using standardized data collection tool. Urine specimens were cultured and interpreted according to standard operating procedures. Data were analyzed using STATA version 11. RESULTS: Out of 402 malnourished underfives, 229 (56.9 %) were male. The median age in months was 17 (IQR; 12-31). Of 402 malnourished underfives, 83 (20.3 %) had significant bacteriuria of gram negative enteric bacteria. Escherichia coli 35/84 and Klebsiella pneumonia 20/84 were predominant bacteria isolated. More than 37 % of isolates were resistant to third generation cephalosporins with all of them exhibiting extended spectrum beta lactamase (ESBL) phenotype. Rates of resistance to ampicillin, amoxillin/clavulanic acid, gentamicin and ciprofloxacin were 82/84 (98.7 %), 47/55 (85.4 %), 45/84 (57.8 %) and 9/84 (10.8 %) respectively. Decrease in age and increase in lymphocytes count were independent factors on multivariate logistic regression analysis found to predict UTI (p<0.05). CONCLUSIONS: Multi-resistant gram negative enteric bacteria are common cause of UTI among underfives. A significant number of severe and moderate malnourished children with bacteriuria had no fever. Therefore, routine testing for UTI is emphasized in all malnourished underfives so that appropriate treatment can be initiated.


Assuntos
Antibacterianos/uso terapêutico , Resistência a Múltiplos Medicamentos , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/epidemiologia , Transtornos da Nutrição do Lactente/complicações , Centros de Atenção Terciária , Infecções Urinárias/epidemiologia , Pré-Escolar , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/complicações , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Lactente , Transtornos da Nutrição do Lactente/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Tanzânia/epidemiologia , Infecções Urinárias/complicações , Infecções Urinárias/tratamento farmacológico
18.
Malar J ; 13: 420, 2014 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-25363545

RESUMO

BACKGROUND: Artemisinin-based combinations currently recommended for treatment of uncomplicated Plasmodium falciparum malaria in many countries of sub-Saharan Africa are substrates of CYP enzymes. The cytochrome enzyme system is responsible for metabolism of about 80-90% of clinically used drugs. It is, therefore, important to obtain the pharmacogenetics of the population in the region with respect to these combinations and thereby enable practitioners to predict treatment outcomes. The aim of this study was to detect and determine allelic frequencies of CYP2C8*2, CYP2C8*3, CYP3A4*1B, CYP3A5*3 and CYP2B6*6 variant alleles in a Tanzanian indigenous population. METHODS: Genomic DNA extraction from blood obtained from 256 participants who escorted patients at Karume Health Centre in Mwanza Tanzania, was carried out using the Gene JET™ Genomic DNA purification kit (Thermo Scientific). Genotyping for the cytochrome P450 variant alleles was performed using predesigned primers. Amplification was done by PCR while differentiation between alleles was done by restriction fragment length polymorphism (PCR-RFLP) (for CYP2C8*2, CYP2C8*3) and sequencing (for CYP2B6*6, CYP3A5*3 and CYP3A4*1B). RESULTS: CYP2C8*2, CYP2C8*3, CYP3A5*3, CYP3A4*1B and CYP2B6*6 variant allelic frequencies were found to be 19,10,16,78 and 36% respectively. CONCLUSION: Prevalence of CYP2C8*2, CYP3A5*3, CYP3A4*1B and CYP2B6*6 mutations in a Tanzanian population/subjects are common. The impact of these point mutations on the metabolism of anti-malarial drugs, particularly artemisinin-based combinations, and their potential drug-drug interactions (DDIs) needs to be further evaluated.


Assuntos
Antimaláricos/farmacocinética , Artemisininas/farmacocinética , Sistema Enzimático do Citocromo P-450/genética , Malária/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Estudos Transversais , Feminino , Frequência do Gene , Humanos , Malária/tratamento farmacológico , Malária/epidemiologia , Masculino , Polimorfismo de Fragmento de Restrição , Tanzânia/epidemiologia , Adulto Jovem
19.
Am J Trop Med Hyg ; 91(4): 833-843, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25048375

RESUMO

Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001 : were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.


Assuntos
Antimaláricos/uso terapêutico , Malária Falciparum/parasitologia , Proteínas de Membrana Transportadoras/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Plasmodium falciparum/genética , Polimorfismo Genético , Proteínas de Protozoários/genética , Substituição de Aminoácidos , Amodiaquina/uso terapêutico , Antimaláricos/farmacologia , Artemeter , Artemisininas/uso terapêutico , Criança , Pré-Escolar , Cloroquina/farmacologia , Conjuntos de Dados como Assunto , Combinação de Medicamentos , Resistência a Medicamentos/genética , Quimioterapia Combinada , Etanolaminas/uso terapêutico , Fluorenos/uso terapêutico , Marcadores Genéticos/genética , Genótipo , Humanos , Lactente , Estimativa de Kaplan-Meier , Lumefantrina , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Fatores de Risco
20.
Acta Trop ; 134: 95-100, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24657845

RESUMO

Most malaria research in sub-Saharan Africa has focused on children and pregnant women, but malaria among hospitalized adults in this region is poorly characterized. In this prospective study, we assessed the prevalence and clinical characteristics of malaria among the inpatient adults in two hospitals in Tanzania. We enrolled adults admitted with suspected malaria and performed routine thick blood smear (BS) and malaria rapid diagnostic tests (RDT). We also assessed malaria parasite clearance rates. We considered malaria status 'confirmed' or 'excluded' only in patients with two concordant tests. Malaria polymerase chain reaction (PCR) was performed in a subset of patients with discordant BS and RDT. After BS and RDT were performed on 579 adults with suspected malaria, malaria was excluded in 458/579 (79.1%) and confirmed in 16/579 (2.8%). One hundred and five out of 579 (18.1%) had discordant results. The prevalences of positive BS and positive RDT were 102/579 (17.6%) and 35/579 (6.0%), respectively, with only fair agreement (Kappa=0.354, p<0.0001). PCR results agreed with RDT in 35/35 (100%) of patients with a negative RDT but positive BS. PCR results also agreed with RDT in 9/13 (69.2%) of cases with a positive RDT but negative BS. Clinical correlates of malaria by multivariable analysis included subjective fever (OR 3.6 [1.0-12.3], p=0.04), headache (OR 3.1 [1.2-8.0], p=0.02) and vomiting (OR 2.7 [1.2-6.4], p=0.02). Malaria parasite clearance was significantly delayed in the HIV-infected group. Our study demonstrated only fair agreement between RDT and BS malaria tests among Tanzanian adult inpatients with suspected malaria. PCR generally agreed with RDT results. HIV was associated with delayed parasite clearance in adults with malaria. We recommend the routine use of RDTs for malaria diagnosis among adults admitted to hospitals in sub-Saharan Africa.


Assuntos
Testes Diagnósticos de Rotina/métodos , Malária/diagnóstico , Malária/epidemiologia , Microscopia/métodos , Parasitologia/métodos , Reação em Cadeia da Polimerase/métodos , Adulto , África ao Sul do Saara , Estudos Transversais , Feminino , Hospitais , Humanos , Pacientes Internados , Malária/patologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Tanzânia/epidemiologia
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