Nutrient Deficiencies and Potential Alteration in Plasma Levels of Naturally Acquired Malaria-Specific Antibody Responses in Tanzanian Children.

Immunoglobulin G (IgG) subclasses have been suggested to confer naturally acquired immunity to Plasmodium falciparum malaria. Cytophilic IgG1 and IgG3 with their potential for opsonization, phagocytosis, and antibody-dependent cellular inhibition in association with monocytes have been suggested to have a critical role in malaria. The potential for production of antibodies is influenced by micronutrient status. This study aimed at exploring the effect of micronutrients, particularly zinc status, on the profiles of IgG subclasses in 304 Tanzanian children aged ≤ 5 years. An enzyme-linked immunosorbent assay was performed using whole asexual blood stage malaria antigens to determine plasma malaria-specific antibody titers. This baseline cross-sectional study was done from 2005 - 2010 prior to the larger randomized control trial of the Micronutrient and Child Health (MACH) Study. Plasma concentrations of zinc and magnesium were measured by inductively coupled plasma atomic emission spectrometry and results correlated with plasma IgG subclass levels. The findings reveal zinc deficiency to possibly influence the production of IgM, total IgG, and several IgG subclasses in a malaria status-dependent manner. Among IgG subclasses, IgG3 and partly IgG2 displayed a remarkable association with zinc deficiency, particularly IgG3 which was predominant in children with malaria. Nevertheless, zinc, magnesium, and malaria status did not influence the association between IgG3 and IgG4. The study leads to the conclusion that, under conditions of micronutrient deficiency and malaria status, an imbalance in IgG subclass production may occur leading to predominantly higher levels of IgG3 and IgG2 that may not confer sufficient protection from infection. The profile of both cytophilic and non-cytophilic IgG subclasses has been shown to be variably influenced by zinc status; the effects vary with age at least in under-fives. These results provide insight for inclusion of micronutrients, particularly precise amounts of zinc, in future malaria interventional programs in endemic areas.

Whole-genome sequencing of SARS-CoV-2 isolates from symptomatic and asymptomatic individuals in Tanzania.

Background: Coronavirus Disease-2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) accounts for considerable morbidity and mortality globally. Paucity of SARS-CoV-2 genetic data from Tanzania challenges in-country tracking of the pandemic. We sequenced SARS-CoV-2 isolated in the country to determine circulating strains, mutations and phylogenies and finally enrich international genetic databases especially with sequences from Africa. Methods: This cross-sectional study utilized nasopharyngeal swabs of symptomatic and asymptomatic adults with positive polymerase chain reaction tests for COVID-19 from January to May 2021. Viral genomic libraries were prepared using ARTIC nCoV-2019 sequencing protocol version three. Whole-genome sequencing (WGS) was performed using Oxford Nanopore Technologies MinION device. In silico genomic data analysis was done on ARTIC pipeline version 1.2.1 using ARTIC nCoV-2019 bioinformatics protocol version 1.1.0. Results: Twenty-nine (42%) out of 69 samples qualified for sequencing based on gel electrophoretic band intensity of multiplex PCR amplicons. Out of 29 isolates, 26 were variants of concern [Beta (n = 22); and Delta (n = 4)]. Other variants included Eta (n = 2) and B.1.530 (n = 1). We found combination of mutations (S: D80A, S: D215G, S: K417N, ORF3a: Q57H, E: P71L) in all Beta variants and absent in other lineages. The B.1.530 lineage carried mutations with very low cumulative global prevalence, these were nsp13:M233I, nsp14:S434G, ORF3a:A99S, S: T22I and S: N164H. The B.1.530 lineage clustered phylogenetically with isolates first reported in south-east Kenya, suggesting regional evolution of SARS-CoV-2. Conclusion: We provide evidence of existence of Beta, Delta, Eta variants and a locally evolving lineage (B.1.530) from samples collected in early 2021 in Tanzania. This work provides a model for ongoing WGS surveillance that will be required to inform on emerging and circulating SARS-CoV-2 diversity in Tanzania and East Africa.

Predictive markers of transmission in areas with different malaria endemicity in north-eastern Tanzania based on seroprevalence of antibodies against Plasmodium falciparum.

OBJECTIVE: A community-based cross-sectional study was done to assess Plasmodium falciparum exposure in areas with different malaria endemicity in north-eastern Tanzania using serological markers; PfAMA-1 and PfMSP-119. RESULTS: Bondo had a higher seroprevalence 36.6% (188) for PfAMA-1 as compared to Hai 13.8% (33), χ2 = 34.66, p < 0.01. Likewise, Bondo had a higher seroprevalence 201(36.6%) for PfMSP-1 as compared to Hai 41 (17.2%), χ2 = 29.62, p < 0.01. Anti-PfAMA-1 titters were higher in malaria positive individuals (n = 47) than in malaria negative individuals (n = 741) (p = 0.07). Anti-PfMSP-1 antibody concentrations were significantly higher in malaria-positive individuals (n = 47) than in malaria-negative individuals (n = 741) (p = 0.003). Antibody response against PfAMA-1 was significantly different between the three age groups; < 5 years, 5 to 15 years and > 15 years in both sites of Bondo and Hai. Likewise, antibody response against PfMSP-119 was significantly different between the three age groups in the two sites (p < 0.001). We also found significant differences in the anti-PfAMA-1and anti-PfMSP-119 antibody concentrations among the three age groups in the two sites (p = 0.004 and 0.005) respectively. Immunological indicators of P. falciparum exposure have proven to be useful in explaining long-term changes in the transmission dynamics, especially in low transmission settings.

Expression analysis of p16 and TOP2A protein biomarkers in cervical cancer lesions and their correlation with clinico-histopathological characteristics in a referral hospital, Tanzania.

INTRODUCTION: Biomarkers yield important information for early diagnosis of cervical cancer. However, they are rarely applied for prognosis of cervical cancer in Tanzania, where visual inspection assay with acetic acid or Lugol's iodine and Pap test are being used as the standard screening/ diagnostic methods. METHODS: This was a retrospective hospital-based cross-sectional study that was conducted to assess cyclin-dependent kinase inhibitor (p16) and topoisomerase II-alpha (TOP2A) proteins expression among women seeking cervical cancer care at Kilimanjaro Christian Medical Centre, Tanzania between May 1, 2017 and May 10, 2018. Immunohistochemistry technique was used to detect the expressions of p16 and TOP2A proteins from the retrieved formalin-fixed and paraffin-embedded (FFPE) cervical biopsies. RESULTS: A total of 145 patients, with a mean age of 52.1 ± 12.9 years, were included in this study. Upon immunohistochemistry staining, 103 (71.0%) and 90 (62.1%) were p16 and TOP2A positive respectively. There was a strong association between histopathological class and p16/TOP2A expression levels (Fisher's exact test, p<0.001). Moreover, there was a strong positive correlation between p16/TOP2A and cancerous cervical lesions (Spearman's rank correlation coefficients = 0.833 and 0.687, p = 0.006 and 0.005, respectively). The age-adjusted odds ratio for predicting cervical cancer lesions were independently significant for p16/TOP2A biomarkers in FFPE cervical tissues [p16: OR = 1.142 (95% CI: 1.059-1.232, p<0.001) and TOP2A: OR = 1.046 (95% CI: 1.008-1.085, p = 0.015)]. Importantly, the diagnostic performance of p16 was higher than that of TOP2A in the diagnosis of cancerous lesions from non-cancerous cervical lesions (sensitivity: 97.2% versus 77.6%, accuracy: 92.8% versus 87.8%, respectively). CONCLUSION: Our study has highlighted that over-expression of TOP2A is related to the grade of cervical intraepithelial neoplasia but does not predict prognosis in cervical cancer. Similarly, expression of p16 is related to degree of histological dysplasia and malignancy, suggesting its prognostic and predictive value in the management of cervical cancers. Further bigger studies are needed to validate their applications in the early diagnosis of cervical cancer.

Detection of Rift Valley Fever virus inter-epidemic activity in Kilimanjaro Region, North Eastern Tanzania.

BACKGROUND: Rift Valley Fever virus (RVFV) is a zoonotic arbovirus of public health impact infecting livestock, wildlife, and humans mainly in Africa and other parts of the world. Despite its public health importance, mechanisms of RVFV maintenance during interepidemic periods (IEPS) remain unclear. OBJECTIVE: We aimed to examine comparatively exposure to RVFV between humans and goats and RVFV infection between humans, goats and mosquitoes. METHODS: A cross sectional study was performed in the Lower Moshi area of the Kilimanjaro region from March to June 2020. RVFV exposure was determined by detecting IgG/IgM to RVFV using a competitive enzyme linked immunosorbent assay whereas infection was determined by real time quantitative polymerase chain reaction (RT-qPCR) assay. RESULTS: Results show that the male gender was related to RVFV seropositivity (χ2 = 5.351; p=0.030). Being 50 years and above was related to seropositivity (χ2 =14.430; p=0.006) whereas bed net use, larger numbers of persons living in the same house (>7 persons) and RVFV seropositivity in goats were related to higher seropositivity to RVFV among humans χ2 =6.003; p=0.021, χ2 =23.213; p < 0.001 and χ2 =27.053; p < 0.001), respectively. By the use of RT-qPCR, goats exhibited the highest RVFV infection rate of 4.1%, followed by humans (2.6%), Ae. aegypti (2.3%), and Cx. pipiens complex(1.5%). Likewise, a higher proportion of goats (23.3%) were RVFV seropositive as compared with humans (13.2%). CONCLUSION: Our findings suggest the Lower Moshi area as a potential hotspot for Rift Valley Fever (RVF), posing the danger of being a source of RVFV spread to other areas. Goats had the highest infection rate, suggesting goats as important hosts for virus maintenance during IEPs. We recommend the implementation of strategies that will warrant active RVF surveillance through the identification of RVF hotspots for targeted control of the disease.

Prevalence and histopathological characterization of Masai Giraffe (Giraffa camelopardalis tippelskirchi) skin disease in Tarangire-Manyara ecosystem, Northern Tanzania.

BACKGROUND: Masai Giraffes have declined dramatically in recent decades due to loss of habitat and illegal hunting. Hence, it is critically important that the epidemiology and etiology of so-called giraffe skin disease (GSD) is understood well. AIM: To assess the prevalence and histopathological characteristics of GSD in the Tarangire-Manyara Ecosystem (TME), northern Tanzania. METHODS: The study used road transects to gather field information on GSD. Eighty-four giraffes were sighted by systematic random sampling in the six study sites. Examination of giraffes involved body distribution of lesions, severity of the lesions and whether they were associated with age and sex of the affected giraffes. Five giraffes with GSD were immobilized for tissue collection and histopathological analysis. RESULTS: Prevalence among adults was 79%. Affected animals typically had 1-5 lesions which were mostly moderate and were predominantly observed on the forelegs. GSD positivity rate was higher among females versus males, whereas males had a higher rate of severe lesions and generally had more lesions than females. Calves showed no lesions. All tissue sections from five affected giraffes showed the presence of large quantities of fungal elements (hyphae and spores) that involved hair shafts and sub-cutaneous tissue after staining with Grocott Methenamine Silver as special fungal staining technique. CONCLUSIONS: Our findings suggest the involvement of fungal infection in GSD pathogenesis. CLINICAL RELEVANCE: We recommend further characterization of the lesions using modern molecular techniques and culture to identify primary and secondary or opportunistic etiologies, and the order in which the pathogens occur in the lesions.

Point prevalence survey of antimicrobial use in three hospitals in North-Eastern Tanzania.

BACKGROUND: Antimicrobial resistance (AMR) is one of the most urgent global health threats with low-resource countries being disproportionately affected. Targeted interventions require insight in antibiotic prescription practices. A point prevalence survey (PPS) is a well-known tool to get insight in antibiotic dispensing practices in hospitals and identify areas for improvement. Here, we describe the results of a PPS performed in a tertiary, regional and district hospital in Kilimanjaro region in Tanzania. METHODS: A PPS was performed in the Kilimanjaro Christian Medical Centre (KCMC; tertiary hospital), Mawenzi (regional) and St. Joseph (district) hospital in November and December 2016. Antibiotic use in all patients admitted more than 24 h and those undergoing surgery was recorded. All clinical wards were included except the pediatrics. Data from a single ward were collected on the same day. RESULTS: A total of 399 patients were included in the PPS: 232 patients from KCMC, 94 from Mawenzi hospital and 73 patients from St. Joseph hospital. Overall prevalence of antibiotic use was 44.0%: 38% in KCMC, 59% in Mawenzi and 63% in St. Joseph. Ceftriaxone (n = 94, 29.8%), metronidazole (n = 79, 23.9%) and other antibiotics belonging to the penicillin class (n = 89, 28.3%) were most commonly prescribed. Antibiotics prescribed for surgical prophylaxis were continued for more than 3 days in 57% of cases. CONCLUSION: Our study shows a rate of broad-spectrum antibiotic use in Tanzanian hospitals and prolonged surgical antibiotic prophylaxis being a common practice. PPS is an important tool to improve future antibiotic use in Tanzania hospitals.

Serological evidence of exposure to Rift Valley, Dengue and Chikungunya Viruses among agropastoral communities in Manyara and Morogoro regions in Tanzania: A community survey.

Tanzania has recently experienced outbreaks of dengue in two coastal regions of Dar es Salaam and Tanga. Chikungunya and Rift Valley Fever outbreaks have also been recorded in the past decade. Little is known on the burden of the arboviral disease causing viruses (Dengue, Rift Valley and Chikungunya) endemically in the inter-epidemic periods. We aimed at determining the prevalence of the dengue, rift valley and chikungunya among humans in two geo ecologically distinct sites. The community-based cross-sectional study was conducted in Magugu in Manyara region and Wami-Dakawa in Morogoro region in Tanzania. Venous blood was collected from participants of all age groups, serum prepared from samples and subjected to ELISA tests for RVFV IgG/IgM, DENV IgG/IgM, and CHIKV IgM/IgG. Samples that were positive for IgM ELISA tests were subjected to a quantitative RT PCR for each virus. A structured questionnaire was used to collect socio-demographic information. Data analysis was performed by using SPSSv22. A total of 191 individuals from both sites participated in the study. Only one individual was CHIKV seropositive in Magugu, but none was seropositive or positive for either RVFV or DENV. Of the 122 individuals from Wami-Dakawa site, 16.39% (n = 20) had recent exposure to RVFV while 9.83% (n = 12) were seropositive for CHIKV. All samples were negative by RVFV and CHIKV qPCR. Neither infection nor exposure to DENV was observed in participants from both sites. Being more than 5 in a household, having no formal education and having recently travelled to an urban area were risk factors associated with RVFV and CHIKV seropositivity. We report a considerable exposure to RVFV and CHIKV among Wami-Dakawa residents during the dry season and an absence of exposure of the viruses among humans in Magugu site. In both sites, neither DENV exposure nor infection was detected.

Prevalence of plasmodium, leptospira and rickettsia species in Northern Tanzania: a community based survey.

BACKGROUND: The overlap of symptoms, geographic and seasonal co-occurrence of Plasmodium, Leptospira and Rickettsia infections makes malaria diagnosis difficult, increasing the chances of misdiagnosis. The paucity of data on the prevalence Plasmodium, Leptospira and Rickettsia infections contributes to an overly diagnosis of malaria. We aimed to determine the prevalence and distribution of Plasmodium, Leptospira and Rickettsia infections in northern Tanzania. METHODS: A community based, cross sectional survey was conducted in two sites in Northern Tanzania. PCR was used to detect Plasmodium, Leptospira and Rickettsia infections. RESULTS: The prevalence of P. falciparum and Leptospira spp were 31/128 (24.2%) and 3/128 (2.3%), respectively. No Rickettsia infection was detected in any of the two sites. Taking study sites separately, Plasmodium infection was detected in 31/63(49.2%) of participants in Bondo while Leptospira infection was detected in 3/65(4.6%) of participants in Magugu. Plasmodium was not detected in Magugu while no Leptospira infections were detected in Bondo. Fever was significantly associated with Plasmodium infection (χ2= 12.44, p<0.001) and age (χ2=17.44, p=0.000). CONCLUSION: Results from this study indicate Plasmodium infection as the main cause of fever in the studied sites. While Plasmodium and Leptospira contribute to fevers, Rickettsia infection is an insignificant cause of fever in Northern Tanzania.

Ceftriaxone use in a tertiary care hospital in Kilimanjaro, Tanzania: A need for a hospital antibiotic stewardship programme.

Excessive use of antibiotics, especially watch group antibiotics such as ceftriaxone leads to emergence and spread of antimicrobial resistance (AMR). In low and middle-income countries (LMICs), antibiotics are overused but data on consumption is scarcely available. We aimed at determining the extent and predictors of ceftriaxone use in a tertiary care university teaching hospital in Kilimanjaro, Tanzania. A hospital-based cross-sectional study was conducted from August 2013 through August 2015. Patients admitted in the medical, surgical wards and their respective intensive care units, receiving antimicrobials and other medications for various ailments were enrolled. Socio-demographic and clinical data were recorded in a structured questionnaire from patients' files and logistic regression was performed to determine the predictors for ceftriaxone use. Out of the 630 patients included in this study, 322 (51.1%) patients were on ceftriaxone during their time of hospitalization. Twenty-two patients out of 320 (6.9%) had been on ceftriaxone treatment without evidence of infection. Ceftriaxone use for surgical prophylaxis was 44 (40.7%), of which 32 (72.7%) and 9 (20.5%) received ceftriaxone prophylaxis before and after surgery, respectively. Three (6.8%) received ceftriaxone prophylaxis during surgery. Predicting factors for that the health facility administered ceftriaxone were identified as history of any medication use before referral to hospital [OR = 3.4, 95% CI (1.0-11.4), p = 0.047], bacterial infection [OR = 18.0, 95% CI (1.4-225.7, p = 0.025)], surgical ward [OR = 2.9, 95% CI (0.9-9.4), p = 0.078] and medical wards [OR = 5.0, 95% CI (0.9-28.3), p = 0.070]. Overall, a high ceftriaxone use at KCMC hospital was observed. Antimicrobial stewardship programs are highly needed to monitor and regulate hospital antimicrobial consumption, which in turn could help in halting the rising crisis of antimicrobial resistance.

Prescription and non-prescription antibiotic dispensing practices in part I and part II pharmacies in Moshi Municipality, Kilimanjaro Region in Tanzania: A simulated clients approach.

Antibiotic dispensing without a prescription poses a threat to public health as it leads to excessive antibiotic consumption. Inappropriate antibiotic availability to the community has been documented to be amongst drivers of antimicrobial resistance emergence. Community pharmacies are a source of antibiotics in low and middle-income countries (LMICs). We aimed at assessing antibiotic dispensing practices by community pharmacy retailers in Moshi urban, Kilimanjaro, Tanzania and recommend interventions to improve practice. Using a Simulated Client (SC) Method, an observational cross-sectional survey of antibiotic dispensing practices was conducted from 10th June to 10th July 2017. Data analysis was done using Stata 13 (StataCorp, College Station, TX, USA). A total of 82 pharmacies were visited. Part I pharmacies were 26 (31.71%) and 56 (68.29%) were part II. Overall 92.3% (95% CI 77.8-97.6) of retailers dispensed antibiotics without prescriptions. The antibiotics most commonly dispensed without a prescription were ampiclox for cough (3 encounters) and azithromycin for painful urination (3 encounters). An oral third generation cephalosporin (cefixime) was dispensed once for painful urination without prescription by a part I pharmacy retailer. Out of 21, 15(71.43%) prescriptions with incomplete doses were accepted and had antibiotics dispensed. Out of 68, 4(5.9%) retailers gave instructions for medicine use voluntarily. None of the retailers voluntarily explained drug side-effects. In Moshi pharmacies, a high proportion of antibiotics are sold and dispensed without prescriptions. Instructions for medicine use are rarely given and none of the retailers explain side effects. These findings support the need for a legislative enforcement of prescription-only antibiotic dispensing rules and regulations. Initiation of clinician and community antibiotic stewardship and educational programs on proper antibiotic use to both pharmacists and public by the regulatory bodies are highly needed.

Prevalence, determinants and knowledge of antibacterial self-medication: A cross sectional study in North-eastern Tanzania.

Self-medication is very common especially in developing countries and is documented to be associated with many health risks including antibiotic resistance. This study investigated the prevalence, determinants and knowledge of self-medication among residents of Siha District in Tanzania. A cross-sectional study was conducted among 300 residents in a rural District of Kilimanjaro region, North-eastern Tanzania from 1st to 28th April 2017. A semi-structured questionnaire was used to collect information regarding drugs used, knowledge, history and reasons for antibiotic self-medication. Log-binomial regression analysis was done using STATA 13 to examine factors associated with self-medication. A slightly majority of the respondents (58%) admitted to self-medication. Antibiotics most commonly utilized were amoxycillin (43%) and an antiprotozoal drug metronidazole (10%). The most common symptoms that led to self-medication were cough (51.17%), headache/ fever/ malaria (25.57%) and diarrhoea (21.59%). The most common reasons for self-medication were emergency illness (24.00%), health facility charges (20.33%), proximity of pharmacy to home (17.00%) and no reason (16.66%). Almost all reported that self-medication is not better than seeking medical consultation, 98% can result into harmful effects and 96% can result to drug resistance. The level of self-medication in this study is comparable with findings from other studies in developing countries. Pharmacies were commonly used as the first point of medical care. There is therefore a need for educative antibiotic legislative intervention to mitigate the adverse effects of antibiotic self-medication in Siha district in Tanzania.

Predictors for Mortality among Multidrug-Resistant Tuberculosis Patients in Tanzania.

PROBLEM: Factors related to MDRTB mortality in Tanzania have not been adequately explored and reported. OBJECTIVES: To determine demographic, clinical, radiographic, and laboratory factors associated with MDRTB mortality in a Tanzanian TB Referral Hospital. METHODOLOGY: This was a cross-sectional study with 193 participants. Demographic, clinical, laboratory, and radiological data were collected, and their associations with mortality among MDRTB patients were determined. RESULTS AND CONCLUSIONS: Cough was the commonest finding among these MDRTB patients, with 179 (92.75%) of them presenting with cough, followed by chest X-ray consolidation in 156 patients (80.83%) and history of previous TB treatment in 151 patients (78.24%). Cigarette smoking, HIV positivity, and low CD4 counts were significantly associated with MDRTB mortality, p values of 0.034, 0.044, and 0.048, respectively. Fever on the other hand was at the borderline with p value of 0.059. We conclude that cigarette smoking and HIV status are significant risk factors for mortality among MDRTB patients. HIV screening should continually be emphasized among patients and the general community for early ARTs initiation. Based on the results from our study, policy makers and public health personnel should consider addressing tobacco cessation as part of national TB control strategy.

Prevalence of dengue and chikungunya virus infections in north-eastern Tanzania: a cross sectional study among participants presenting with malaria-like symptoms.

BACKGROUND: In spite of increasing reports of dengue and chikungunya activity in Tanzania, limited research has been done to document the general epidemiology of dengue and chikungunya in the country. This study aimed at determining the sero-prevalence and prevalence of acute infections of dengue and chikungunya virus among participants presenting with malaria-like symptoms (fever, headache, rash, vomit, and joint pain) in three communities with distinct ecologies of north-eastern Tanzania. METHODS: Cross sectional studies were conducted among 1100 participants (aged 2-70 years) presenting with malaria-like symptoms at health facilities at Bondo dispensary (Bondo, Tanga), Hai hospital (Hai, Kilimanjaro) and TPC hospital (Lower Moshi). Participants who were malaria negative using rapid diagnostic tests (mRDT) were screened for sero-positivity towards dengue and chikungunya Immunoglobulin G and M (IgG and IgM) using ELISA-based kits. Participants with specific symptoms defined as probable dengue and/or chikungunya by WHO (fever and various combinations of symptoms such as headache, rash, nausea/vomit, and joint pain) were further screened for acute dengue and chikungunya infections by PCR. RESULTS: Out of a total of 1100 participants recruited, 91.2 % (n = 1003) were malaria negative by mRDT. Out of these, few of the participants (<5 %) were dengue IgM or IgG positive. A total of 381 participants had fever out of which 8.7 % (33/381) met the defined criteria for probable dengue, though none (0 %) was confirmed to be acute cases. Chikungunya IgM positives among febrile participants were 12.9 % (49/381) while IgG positives were at 3.7 % (14/381). A total of 74.2 % (283/381) participants met the defined criteria for probable chikungunya and 4.2 % (11/263) were confirmed by PCR to be acute chikungunya cases. Further analyses revealed that headache and joint pain were significantly associated with chikungunya IgM seropositivity. CONCLUSION: In north-eastern Tanzania, mainly chikungunya virus appears to be actively circulating in the population. Continuous surveillance is needed to determine the contribution of viral infections of fever cases. A possible establishment of arboviral vector preventive control measures and better diagnosis of pathogens to avoid over-treatment of other diseases should be considered.

Effect of nutrient deficiencies on in vitro Th1 and Th2 cytokine response of peripheral blood mononuclear cells to Plasmodium falciparum infection.

BACKGROUND: An appropriate balance between pro-inflammatory and anti-inflammatory cytokines that mediate innate and adaptive immune responses is required for effective protection against human malaria and to avoid immunopathology. In malaria endemic countries, this immunological balance may be influenced by micronutrient deficiencies. METHODS: Peripheral blood mononuclear cells from Tanzanian preschool children were stimulated in vitro with Plasmodium falciparum-parasitized red blood cells to determine T-cell responses to malaria under different conditions of nutrient deficiencies and malaria status. RESULTS: The data obtained indicate that zinc deficiency is associated with an increase in TNF response by 37%; 95% CI: 14% to 118% and IFN-gamma response by 74%; 95% CI: 24% to 297%. Magnesium deficiency, on the other hand, was associated with an increase in production of IL-13 by 80%; 95% CI: 31% to 371% and a reduction in IFN-gamma production. These results reflect a shift in cytokine profile to a more type I cytokine profile and cell-cell mediated responses in zinc deficiency and a type II response in magnesium deficiency. The data also reveal a non-specific decrease in cytokine production in children due to iron deficiency anaemia that is largely associated with malaria infection status. CONCLUSIONS: The pathological sequels of malaria potentially depend more on the balance between type I and type II cytokine responses than on absolute suppression of these cytokines and this balance may be influenced by a combination of micronutrient deficiencies and malaria status.