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.

Africa's oesophageal cancer corridor: Do hot beverages contribute?

PURPOSE: Hot beverage consumption has been linked to oesophageal squamous cell cancer (EC), but its contribution to the poorly understood East African EC corridor is not known. METHODS: In a cross-sectional study of general-population residents in Kilimanjaro, North Tanzania, tea drinking temperatures and times were measured. Using linear regression models, we compared drinking temperatures to those in previous studies, by socio-demographic factors and tea type ("milky tea" which can be 50 % or more milk and water boiled together vs "black tea" which has no milk). RESULTS: Participants started drinking at a mean of 70.6 °C (standard deviation 3.9, n = 188), which exceeds that in all previous studies (p ≤ 0.01 for each). Tea type, gender and age were associated with drinking temperatures. After mutual adjustment for each other, milky tea drinkers drank their tea 1.9 °C (95 % confidence interval: 0.9, 2.9) hotter than drinkers of black tea, largely because black tea cooled twice as fast as milky tea. Men commenced drinking tea 0.9 °C (-0.2, 2.1) hotter than women did and finished their cups 30 (-9, 69) seconds faster. 70 % and 39 % of milky and black tea drinkers, respectively, reported a history of tongue burning. CONCLUSIONS: Hot tea consumption, especially milky tea, may be an important and modifiable risk factor for EC in Tanzania. The contribution of this habit to EC risk needs to be evaluated in this setting, jointly with that of the many risk factors acting synergistically in this multi-factorial disease.

Nevirapine concentrations in saliva measured by thin layer chromatography and self-reported adherence in patients on antiretroviral therapy at Kilimanjaro Christian Medical Centre, Tanzania.

BACKGROUND: Thin layer chromatography (TLC) can be used to perform therapeutic drug monitoring in resource-limited settings, where more expensive analytical methods, such as high-performance liquid chromatography or liquid chromatography-mass spectrometry, are not feasible. OBJECTIVES: The aim of this cross-sectional study was to compare saliva concentrations of nevirapine (NVP) with self-reported adherence in patients on NVP-containing antiretroviral treatment at Kilimanjaro Christian Medical Centre, Moshi, Tanzania. METHODS: HIV-infected patients using a combination of zidovudine + lamivudine + NVP, or stavudine + lamivudine + NVP, for more than 4 weeks were included. Saliva samples were collected using dental cotton rolls impregnated with citric acid (20 mg). Saliva NVP concentrations were analyzed using TLC. Adherence to ARV medication was assessed by self-reporting using the Morisky scale. RESULTS: Of the 91 study participants, 79 (86.8%) had therapeutic saliva NVP concentrations (ie, >1.75 mg/L) and 12 (13.2%) had subtherapeutic concentrations. Self-reported adherence among the study participants was high in 62 participants (68.1%), moderate in 24 (26.4%), and low in 5 (5.5%). Fifty-seven (91.9%) of the study participants with high self-reported adherence had therapeutic saliva NVP concentrations. Of the 5 participants with low self-reported adherence, 3 had therapeutic NVP concentrations. CONCLUSIONS: A high proportion of patients had therapeutic NVP saliva concentrations as measured by TLC, which showed a good agreement with self-reported adherence.

Residual Plasmodium falciparum parasitemia in Kenyan children after artemisinin-combination therapy is associated with increased transmission to mosquitoes and parasite recurrence.

BACKGROUND: Parasite clearance time after artemisinin-based combination therapy (ACT) may be increasing in Asian and African settings. The association between parasite clearance following ACT and transmissibility is currently unknown. METHODS: We determined parasite clearance dynamics by duplex quantitative polymerase chain reaction (qPCR) in samples collected in the first 3 days after treatment of uncomplicated malaria with ACT. Gametocyte carriage was determined by Pfs25 quantitative nucleic acid sequence-based amplification assays; infectiousness to mosquitoes by membrane-feeding assays on day 7 after treatment. RESULTS: Residual parasitemia was detected by qPCR in 31.8% (95% confidence interval [CI], 24.6-39.8) of the children on day 3 after initiation of treatment. Residual parasitemia was associated with a 2-fold longer duration of gametocyte carriage (P = .0007), a higher likelihood of infecting mosquitoes (relative risk, 1.95; 95% CI, 1.17-3.24; P = .015), and a higher parasite burden in mosquitoes (incidence rate ratio, 2.92; 95% CI, 1.61-5.31; P < .001). Children with residual parasitemia were also significantly more likely to experience microscopically detectable parasitemia during follow-up (relative risk, 11.25; 95% CI, 4.08-31.01; P < .001). CONCLUSIONS: Residual submicroscopic parasitemia is common after ACT and is associated with a higher transmission potential. Residual parasitemia may also have consequences for individual patients because of its higher risk of recurrent parasitemia.

Cryptococcal antigen prevalence in HIV-infected Tanzanians: a cross-sectional study and evaluation of a point-of-care lateral flow assay.

OBJECTIVES: Cryptococcal antigen (CRAG) screening at antiretroviral therapy (ART) initiation and pre-emptive antifungal treatment for those testing positive could prevent many cases of cryptococcal meningitis (CM). To investigate whether CRAG screening would be feasible in Tanzania, we conducted a cross-sectional study measuring CRAG prevalence in ART clinic patients and comparing the novel lateral flow assay (LFA) with the cryptococcal latex agglutination (LA) test. METHODS: Consecutive HIV-infected outpatients with CD4 counts <200 cells/µL, who were ART naive or had been on ART for <6 months, were screened for CRAG using the LA and LFA kits. For further assay validation, HIV-infected inpatients with suspected cryptococcal disease were also tested using the LA and LFA kits. RESULTS: Cryptococcal antigen was detected in seven of 218 ART clinic attendees (3%). Six patients (5%) with CD4 cell counts ≤100 cells/µL (n = 124) were CRAG-positive. Agreement between the LA and LFA test in the 218 outpatients was 100%. Another 101 inpatients were tested for CRAG, of whom 56 (55%) were CRAG-positive on both the LA and LFA tests. One patient was positive using the LFA test but negative on the LA test. The overall agreement between the two assays was 99.7%, kappa coefficient 0.99 (standard error 0.06, P < 0.001). CONCLUSIONS: Five percentage of ART clinic patients with CD4 cell counts ≤100 cells/µL in northern Tanzania had asymptomatic cryptococcal antigenaemia, suggesting that CRAG screening would be worthwhile in the Tanzanian ART programme. The LFA is a reliable, cheap and practical alternative to LA for detection of CRAG.

Trends in chloroquine resistance marker, Pfcrt-K76T mutation ten years after chloroquine withdrawal in Tanzania.

BACKGROUND: Plasmodium falciparum resistance to anti-malarial drugs remains a major obstacle to the control of malaria. In 2001 Tanzania replaced chloroquine (CQ) with sulphadoxine-pyrimethamine (SP) as first-line drug, which in turn was replaced by artemisinin combination therapy in 2006. SP has however, continued to be used in intermittent preventive treatment of malaria in pregnancy (IPTp) despite reports of high levels of resistance to SP due to the lack of alternatives to SP for IPTp. Recent reports have indicated recovery of CQ-susceptibility in Malawi, Kenya, Mozambique, and Tanzania based on the prevalence of wild types at codon 76 of the Pfcrt gene in indigenous P. falciparum populations. The current prevalence of this Pfcrt-76 CQ resistance marker from six regions of Tanzania mainland is hereby reported. METHODS: DNA extracted from filter-paper dried blood spots and rapid diagnostics kit strips collected from finger-prick blood were used to genotype the Pfcrt-76 resistance marker using PCR-RFLP. Data from previously published studies were used to generate CQ susceptibility recovery trends using logistic regression model. RESULTS: Seven hundred and forty one (741) samples were genotyped. The current frequency of the CQ-susceptible Pfcrt-K76 was above 92% and did not differ between regions in Tanzania (χ(2) = 2.37; p = 0.795). The K76 allelic prevalence was between 85.7 and 93% in regions (χ(2) = 7.88, p = 0.163). The CQ resistance recovery trends showed regional variability that may be caused by differences in malaria transmission intensity, but overall the trends converge as the susceptibility levels in all regions approach >90%. CONCLUSIONS: CQ withdrawal in Tanzania has resulted into >90% recovery of susceptibility in ten years of withdrawal. These findings are in support of the search for CQ-based combination drugs as a possible future alternative to SP for IPTp in places where full recovery of CQ-susceptibility will be evident.

Malaria diagnostic testing and treatment practices in three different Plasmodium falciparum transmission settings in Tanzania: before and after a government policy change.

BACKGROUND: Patterns of decreasing malaria transmission intensity make presumptive treatment of malaria an unjustifiable approach in many African settings. The controlled use of anti-malarials after laboratory confirmed diagnosis is preferable in low endemic areas. Diagnosis may be facilitated by malaria rapid diagnostic tests (RDTs). In this study, the impact of a government policy change, comprising the provision of RDTs and advice to restrict anti-malarial treatment to RDT-positive individuals, was assessed by describing diagnostic behaviour and treatment decision-making in febrile outpatients <10 years of age in three hospitals in the Kagera and Mwanza Region in northern Tanzania. METHODS: Prospective data from Biharamulo and Rubya Designated District Hospital (DDH) were collected before and after policy change, in Sumve DDH no new policy was implemented. Diagnosis of malaria was confirmed by RDT; transmission intensity was evaluated by a serological marker of malaria exposure in hospital attendees. RESULTS: Prior to policy change, there was no evident association between the actual level of transmission intensity and drug-prescribing behaviour. After policy change, there was a substantial decrease in anti-malarial prescription and an increase in prescription of antibiotics. The proportion of parasite-negative individuals who received anti-malarials decreased from 89.1% (244/274) to 38.7% (46/119) in Biharamulo and from 76.9% (190/247) to 10.0% (48/479) in Rubya after policy change. CONCLUSION: This study shows that an official policy change, where RDTs were provided and healthcare providers were advised to adhere to RDT results in prescribing drugs can be followed by more rational drug-prescribing behaviour. The current findings are promising for improving treatment policy in Tanzanian hospitals.

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.

Herpes Simplex virus type 2 seroprevalence and risk factors among adolescents and youth with HIV-1 in Northern, Tanzania.

INTRODUCTION: Herpes Simplex virus type 2 (HSV-2) infection is associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) acquisition and transmission. Individuals co-infected with HIV-1 and HSV-2 may have longer lasting, more frequent and severe outbreaks of herpes symptoms. Previous studies have assessed HSV-2 seroprevalence and associated risk factors in adult populations. However, there is limited data on the HSV-2 seroprevalence among adolescents and youth living with HIV-1. The study aimed to determine the HSV-2 seroprevalence and associated risk factors among adolescents and youth living with HIV-1 at referral hospital setting in Northern Tanzania. METHODOLOGY: A cross-sectional survey was conducted between February and July 2017 among HIV-1-infected individuals aged 10-24 years attending the Child -Centred Family Care Clinic at Kilimanjaro Christian Medical Centre. Blood specimens from 180 individuals were collected for ELISA-based detection of HSV-2 antibodies. Associations between risk factors and HSV-2 seroprevalence were analysed by univariate and multivariate logistic regression models. RESULTS: The overall HSV-2 seroprevalence was 18% (32/180). A significant HSV-2 seroprevalence was noted among adolescents and youth, who reported having had sexual intercourse than those who never had sexual intercourse (28.9% vs 13.3%, p = 0.02). Youths aged 20-24 had six folds higher risk of HSV-2 seroprevalence compared to those aged 10-14 years (AOR = 5.97 95% CI 1.31 - 27.19, p = 0.02). CONCLUSIONS: Our study found that HSV-2 seroprevalence increased by age among adolescents and youth living with HIV-1. Age-specific approaches might play an important role in interventions targeting HSV-2 infection.

Overuse of artemisinin-combination therapy in Mto wa Mbu (river of mosquitoes), an area misinterpreted as high endemic for malaria.

BACKGROUND: Adequate malaria diagnosis and treatment remain major difficulties in rural sub-Saharan Africa. These issues deserve renewed attention in the light of first-line treatment with expensive artemisinin-combination therapy (ACT) and changing patterns of transmission intensity. This study describes diagnostic and treatment practices in Mto wa Mbu, an area that used to be hyperendemic for malaria, but where no recent assessments of transmission intensity have been conducted. METHODS: Retrospective and prospective data were collected from the two major village health clinics. The diagnosis in prospectively collected data was confirmed by microscopy. The level of transmission intensity was determined by entomological assessment and by estimating sero-conversion rates using anti-malarial antibody responses. RESULTS: Malaria transmission intensity by serological assessment was equivalent to < 1 infectious bites per person per year. Despite low transmission intensity, > 40% of outpatients attending the clinics in 2006-2007 were diagnosed with malaria. Prospective data demonstrated a very high overdiagnosis of malaria. Microscopy was unreliable with < 1% of slides regarded as malaria parasite-positive by clinic microscopists being confirmed by trained research microscopists. In addition, many 'slide negatives' received anti-malarial treatment. As a result, 99.6% (248/249) of the individuals who were treated with ACT were in fact free of malaria parasites. CONCLUSION: Transmission intensity has dropped considerably in the area of Mto wa Mbu. Despite this, most fevers are still regarded and treated as malaria, thereby ignoring true causes of febrile illness and over-prescribing ACT. The discrepancy between the perceived and actual level of transmission intensity may be present in many areas in sub-Saharan Africa and calls for greater efforts in defining levels of transmission on a local scale to help rational drug-prescribing behaviour.

Prevalence of Plasmodium falciparum and Salmonella typhi Infection and Coinfection and Their Association With Fever in Northern Tanzania.

BACKGROUND: Plasmodium falciparum and Salmonella typhi are major causes of fever in the tropics. Although these infections are caused by different organisms and are transmitted via different mechanisms, they have similar epidemio-logic and clinical features. This study aimed to determine the prevalence of S. typhi and P. falciparum infections and their associations with fever at 2 sites in Northern Tanzania. METHODS: This was a community-based, cross-sectional study, conducted from February to June 2016, involving 128 randomly selected individuals, aged between 1 and 70 years. Sixty-three (49.2%) participants were recruited from Bondo Ward, Tanga Region, and 65 (50.8%) were recruited from Magugu Ward, Manyara Region. Blood samples were collected by venepuncture into sterile microtubes. Detection of pathogen DNA was achieved via a multiplex real-time polymerase chain reaction assay. Data analysis was done using Stata, version 14. Prevalence data were presented as numbers and percentages, and chi-square analysis was used to assess associations. P values of .05 or less were considered statistically significant. RESULTS: Of 128 participants, 31 (24.2%) and 17 (13.3%) tested positive for P. falciparum and S. typhi infection, respectively. Of the 63 participants from Bondo, 31 (49.2%) had P. falciparum parasitaemia. None of the participants from Magugu tested positive for Plasmodium parasitaemia. S. typhi bacteraemia was detected in 11 (17.5%) of 63 and 6 (9.2%) of 65 participants in Bondo and Magugu, respectively. P. falciparum-S. typhi coinfection was only detected in Bondo (n=6, 9.5%). Age was the only variable that showed a significant association with both P. falciparum and S. typhi infection; falling within the 5-to 9-year or 10-to 15-year age groups was associated with both infections (X2=2.1; P=.045). Among the 30 patients with Plasmodium parasitaemia, 7 (23.3%) had fever, whereas 2 (12.5%) of 16 patients infected by S. typhi had fever. P. falciparum infection (X2=12.4, P<.001) and P. falciparum-S. typhi coinfection (X2=5.5, P=.019) were significantly associated with fever, while S. typhi infection alone was not. CONCLUSION: S. typhi and P. falciparum were considerably prevalent in the area. One-third of the P. falciparum-S. typhi coinfected individuals in Bondo had fever. P. falciparum infection was an important contributor to febrile illness in Bondo. In the presence of coinfections with P. falciparum and S. typhi, the use of malaria rapid diagnostic tests should be emphasised to reduce irrational use of medications.

Toxoplasma gondii seroprevalence among pregnant women attending antenatal clinic in Northern Tanzania.

BACKGROUND: Acute Toxoplasma gondii infection during pregnancy represents a risk for congenital disease, especially among women without previous exposure to infection. There is, however, a paucity of information about the epidemiology of T. gondii infection in pregnant women in Tanzania. This study aimed to determine the seroprevalence of T. gondii infection and associated demographic, clinical, and behavioral risk factors in pregnant women attending ante-natal clinic (ANC) at Kilimanjaro Christian Medical Center (KCMC), a referral medical center in Northern Tanzania. METHODS: A hospital-based cross-sectional study was carried out from 1 February to 30 April 2017. Data on maternal demographic characteristics, obstetric history, knowledge, and practices related to T. gondii infection were collected from 254 pregnant women attending antenatal care at KCMC. A sample of 4 mL of blood was collected from each participant and sera prepared from each sample. Serum samples were tested for the presence of specific T. gondii IgG and IgM antibodies by indirect Enzyme-Linked Immunosorbent Assay (ELISA). DNA was extracted from whole blood for polymerase chain reaction (PCR) testing, targeting the DNA sequence coding for the Internal Transcribed Spacer 1 (ITS1). RESULTS: The overall T. gondii seroprevalence, including both IgM- and IgG-positive individuals, was 44.5%. Of the 254 tested women, 102 and 23 were seropositive for T. gondii-specific IgG and IgM antibodies respectively and 113 individuals had antibodies of either or both classes. All IgM-positive samples were also tested by PCR, and all were negative. The majority (90%) of the women surveyed had never heard about toxoplasmosis. Consumption of raw vegetables [aOR = 0. 344; 95% CI 0.151-0.784; p = 0.011] and having regular contact with soil [aOR = 0.482; 95% CI 0.268-0.8681; p = 0.015] were both associated with T. gondii antibody status. Inverse relationships with probability of T. gondii exposure were observed, such that these practices were associated with reduced probability of antibody detection. CONCLUSION: Based on serology results, we report widespread exposure to T. gondii infection among pregnant women attending ANC in KCMC. The complex interaction of risk factors for T. gondii infection needs to be studied in larger longitudinal studies.

Naturally Acquired Antibody Responses to a Synthetic Malaria Antigen AS202.11.

BACKGROUND: A major challenge to malaria vaccine development is identification of protective epitopes and respective protective immune responses. OBJECTIVE: To characterize naturally acquired Immunoglobulin G (IgG) responses to the synthetic peptide AS202.11, a malaria vaccine candidate. METHODOLOGY: This community based cross-sectional study enrolled 320 participants aged 1 year and above. Demographic information was recorded through interviews. Detection of P. falciparum infection was done by microscopy, malaria rapid diagnostic test, and polymerase chain reaction. ELISA was used to detect IgG antibody. Data was analyzed using STATA. RESULTS: The overall AS202.11 IgG seropositivity was 78.8% (73.9-82.9). Seropositivity by age categories was ≤12 years [74.3% (67.4-80.2)], 13-40 years [85.3% (76.5-91.1)], and >40 years [82.6% (68.7-91.1)]. Compared to the ≤ 12-year-old group, aORs for the other groups were 2.22 (1.14-4.32), p = 0.019, and 1.87 (0.81-4.35), p = 0.143, for the 13-40-year-old and >40-year-old groups, respectively. The 13-40-year-old group had more seropositive individuals compared to the ≤ 12-year-old group. CONCLUSION: We report a high degree of recognition of AS202.11 by IgG elicited by field P. falciparum strains, suggesting its close similarity to native P. falciparum antigens and possible suitability of the peptide as a future malaria vaccine candidate.

Occurrence of pfatpase6 Single Nucleotide Polymorphisms Associated with Artemisinin Resistance among Field Isolates of Plasmodium falciparum in North-Eastern Tanzania.

We aimed to determine the current prevalence of four P. falciparum candidate artemisinin resistance biomarkers L263E, E431K, A623E, and S769N in the pfatpase6 gene in a high transmission area in Tanzania in a retrospective cross sectional study using 154 archived samples collected from three previous malaria studies in 2010, 2011 and 2013. Mutations in pfatpase6 gene were detected in parasite DNA isolated from Dried Blood Spots by using PCR-RFLP. We observed overall allelic frequencies for L263E, E431K, A623E, and S769N to be 5.8% (9/154), 16.2% (25/154), 0.0% (0/154), and 3.9% (6/154). The L263E mutation was not detected in 2010 but occurred at 3.9% and 2.6% in 2011 and 2013 respectively. The L263E mutation showed a significant change of frequency between 2010 and 2011, but not between 2011 and 2013 (P < 0.05). Frequency of E431K was highest of all without any clear trend whereas S769N increased from 2.2% in 2010 to 3.6% in 2011 and 5.1% in 2013. A623E mutation was not detected. The worrisome detection and the increase in the frequency of S769N and other mutations calls for urgent assessment of temporal changes of known artemisinin biomarkers in association with in vivo ACT efficacy.

Efavirenz, tenofovir and emtricitabine combined with first-line tuberculosis treatment in tuberculosis-HIV-coinfected Tanzanian patients: a pharmacokinetic and safety study.

BACKGROUND: To evaluate the effect of rifampicin-based tuberculosis (TB) treatment on the pharmacokinetics of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet, and vice versa, in Tanzanian TB-HIV-coinfected patients. METHODS: This was a Phase II open-label multiple dose pharmacokinetic and safety study. This study was conducted in TB-HIV-coinfected Tanzanian patients who started TB treatment (rifampicin/isoniazid/pyrazinamide/ethambutol) at week 1 to week 8 and continued with rifampicin and isoniazid for another 16 weeks. Antiretroviral treatment (ART) of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet was started at week 4 after initiation of TB treatment. A 24-h pharmacokinetic sampling curve was recorded at week 8 (with TB treatment) and week 28 (ART alone). For TB drugs, blood samples at 2 and 5 h post-dose were taken at week 3 (TB treatment alone) and week 8 (with ART). RESULTS: A total of 25 patients (56% male) completed the study; 21 had evaluable pharmacokinetic profiles. The area under the concentration-time curve 0-24 h post-dose of efavirenz, tenofovir and emtricitabine were slightly higher when these drugs were coadministered with TB drugs; geometric mean ratios (90% CI) were 1.08 (0.90, 1.30), 1.13 (0.93, 1.38) and 1.05 (0.85, 1.29), respectively. For TB drugs, equivalence was suggested for peak plasma concentrations when administered with and without efavirenz/tenofovir/emtricitabine. Adverse events were mostly mild and no serious adverse events or drug discontinuations were reported. CONCLUSIONS: Coadministration of efavirenz, tenofovir and emtricitabine with a standard first-line TB treatment regimen did not significantly alter the pharmacokinetic parameters of these drugs and was tolerated well by Tanzanian TB patients who are coinfected with HIV.

Defining malaria burden from morbidity and mortality records, self treatment practices and serological data in Magugu, Babati District, northern Tanzania.

Malaria morbidity and mortality data from clinical records provide essential information towards defining disease burden in the area and for planning control strategies, but should be augmented with data on transmission intensity and serological data as measures for exposure to malaria. The objective of this study was to estimate the malaria burden based on serological data and prevalence of malaria, and compare it with existing self-treatment practices in Magugu in Babati District of northern Tanzania. Prospectively, 470 individuals were selected for the study. Both microscopy and Rapid Diagnostic Test (RDT) were used for malaria diagnosis. Seroprevalence of antibodies to merozoite surface proteins (MSP-1(19)) and apical membrane antigen (AMA-1) was performed and the entomological inoculation rate (EIR) was estimated. To complement this information, retrospective data on treatment history, prescriptions by physicians and use of bed nets were collected. Malaria prevalence in the area was 6.8% (32/470). Of 130 individuals treated with artemisinin combination therapy (ACT), 22.3% (29/130) were slide confirmed while 75.3% (98/130) of them were blood smear negative. Three of the slides confirmed individuals were not treated with ACT. Fever was reported in 38.2% of individuals, of whom 48.8% (88/180) were given ACT. Forty-two (32.3%) of those who received ACT had no history of fever. About half (51.1%) of those treated with ACT were children < 10 years old. Immunoglobulin against MSP-119 was positive in 16.9% (74/437) while against AMA-1 was positive in 29.8% (130/436). Transmission intensity was estimated at <0.2 infectious bites per person per year. The RDT was highly specific (96.3%) but with low sensitivity (15.6%). In conclusion, Magugu is a low endemic area. There is substantial over diagnosis, over treatment and self treatment in the community. The burden of malaria based on medical records is over estimated as was mostly presumptive. The low sensitivity of RDT reflects the low number of immune individuals as well as the low parasite density.

Primaquine clears submicroscopic Plasmodium falciparum gametocytes that persist after treatment with sulphadoxine-pyrimethamine and artesunate.

BACKGROUND: P. falciparum gametocytes may persist after treatment with sulphadoxine-pyrimethamine (SP) plus artesunate (AS) and contribute considerably to malaria transmission. We determined the efficacy of SP+AS plus a single dose of primaquine (PQ, 0.75 mg/kg) on clearing gametocytaemia measured by molecular methods. METHODOLOGY: The study was conducted in Mnyuzi, an area of hyperendemic malaria in north-eastern Tanzania. Children aged 3-15 years with uncomplicated P. falciparum malaria with an asexual parasite density between 500-100,000 parasites/microL were randomized to receive treatment with either SP+AS or SP+AS+PQ. P. falciparum gametocyte prevalence and density during the 42-day follow-up period were determined by real-time nucleic acid sequence-based amplification (QT-NASBA). Haemoglobin levels (Hb) were determined to address concerns about haemolysis in G6PD-deficient individuals. RESULTS: 108 individuals were randomized. Pfs25 QT-NASBA gametocyte prevalence was 88-91% at enrolment and decreased afterwards for both treatment arms. Gametocyte prevalence and density were significantly lower in children treated with SP+AS+PQ. On day 14 after treatment 3.9% (2/51) of the SP+AS+PQ treated children harboured gametocytes compared to 62.7% (32/51) of those treated with SP+AS (p<0.001). Hb levels were reduced in the week following treatment with SP+AS+PQ and this reduction was related to G6PD deficiency. The Hb levels of all patients recovered to pre-treatment levels or greater within one month after treatment. CONCLUSIONS: PQ clears submicroscopic gametocytes after treatment with SP+AS and the persisting gametocytes circulated at densities that are unlikely to contribute to malaria transmission. For individuals without severe anaemia, addition of a single dose of PQ to an efficacious antimalarial drug combination is a safe approach to reduce malaria transmission following treatment. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN61534963.