Tuberculosis symptom screening for children and adolescents living with HIV in six high HIV/TB burden countries in Africa.

OBJECTIVES: The WHO recommends that children and adolescents living with HIV (CALHIV) complete TB symptom screening at every clinical encounter but evidence supporting this recommendation is limited. We evaluated the performance of the recommended TB symptom screening in six high-burden TB/HIV countries. DESIGN: Retrospective longitudinal cohort. METHODS: We extracted data from electronic medical records of CALHIV receiving care from clinics in Botswana, Eswatini, Lesotho, Malawi, Tanzania, and Uganda from January 2014 to June 2017. We defined incident TB cases as those prescribed TB treatment within 30 days of TB diagnosis. We analyzed the most recent symptom screen preceding a TB diagnosis. In accordance with WHO guidelines, positive screens were defined as current fever, cough, poor weight gain, or recent TB contact. Odds of TB disease was modeled by screen result and age at which screening was conducted. RESULTS: Twenty thousand seven hundred and six patients collectively had 316 740 clinic visits, of which 240 161 (75.8%) had documented TB symptom screens. There were 35 701 (14.9%) positive TB symptom screens, and 1212 incident TB diagnoses. Sensitivity and specificity of the TB symptom screen to diagnose TB were 61.2% (95% CI 58.4--64.0) and 88.8% (95% CI 88.7--88.9), respectively. Log odds of documented TB for positive or negative screens was statistically different only for screens conducted at ages 7--17. CONCLUSION: Although specificity was high, the sensitivity of the TB symptom screen to detect TB in CALHIV was low. More accurate screening approaches are needed to optimally identify TB disease in CALHIV.

Pharmaceutical Dosing Errors at a Pediatric HIV Clinic in Mwanza, Tanzania.

The outpatient medication dosing error rate at a pediatric HIV clinic in Mwanza, Tanzania, was about 1 in every 34 prescriptions. Young children were at highest risk of a dosing error likely because of dose changes with growth and also the inconsistent supply of pediatric formulations. Majority of errors occurred at consecutive visits suggesting clinicians reordered medication without double checking dosing.

Antiretroviral Therapy in Children Less Than 24 Months of Age at Pediatric HIV Centers in Tanzania: 12-Month Clinical Outcomes and Survival.

BACKGROUND: Without antiretroviral therapy (ART), approximately one-half of HIV-infected infants will die by two years. In 2010, the World Health Organization (WHO) recommended that all HIV-infected infants < 24 months be initiated on ART regardless of their clinical/immunologic status. However, there remains little published data detailing cohorts of infants on ART in Sub-Saharan Africa. This study describes baseline characteristics and 12 month outcomes of a cohort of HIV-infected children < 24 months of age at pediatric HIV centers in Mwanza and Mbeya, Tanzania. MATERIALS AND METHODS: Retrospective chart review. INCLUSION CRITERIA: children < 24 months of age, initiated on ART at Baylor Children s Foundation Tanzania clinics, between March-December 2011. RESULTS: Baseline: Ninety-three children were initiated on ART at a median age of 13.4 months. Sixty-seven percent had severe immunosuppression and 31.5% had severe malnutrition. OUTCOME: Seventy-three patients were still in care at 12 month follow-up, there were four (4.3%) deaths, five (5.4%) patients transferred, and 11 (11.8%) loss to follow-up. Average CD4% was 32.7 (p < 0.001). Ninety percent of patients were WHO treatment stage I (p < 0.001). Eighty-six percent had normal nutritional status (p < 0.001). CONCLUSION: Our cohort of HIV infected children < 24 months initiated on ART did well clinically at 12 month outcomes despite being severely immunocompromised and malnourished at baseline. Nevirapine based regimens had good 12 month clinical outcomes, regardless of maternal exposure. Loss to follow-up rate was high for our cohort, demonstrating the need to develop strong mechanisms to counteract this.

Malaria and HIV among pediatric inpatients in two Tanzanian referral hospitals: A prospective study.

Malaria remains common in sub-Saharan Africa, but it is frequently over-diagnosed and over-treated in hospitalized children. HIV is prevalent in many malaria endemic areas and may delay parasite clearance and increase mortality among children with malaria. This prospective cohort study enrolled children with suspected malaria between 3 months and 12 years of age hospitalized at two referral hospitals in Tanzania. Both a thick blood smear (BS) and a malaria rapid diagnostic test (mRDT) were performed. If discordant results were obtained, PCR was performed for Plasmodium falciparum. Malaria was confirmed if two out of three tests were positive. Malaria parasite densities were determined for two consecutive days after diagnosis and treatment of malaria. All participants were tested for HIV. Among 1492 hospitalized children, 400 (26.8%) were enrolled with suspected malaria infection. There were 196/400 (49.0%) males, and the median age was 18 [9-36] months. BS was positive in 95/400 (23.8%), and mRDT was positive in 70/400 (17.5%), with moderate agreement (Kappa=0.598). Concordant results excluded malaria in 291/400 (72.8%) and confirmed malaria in 56/400 (14.0%). PCR performed on 53 discordant results confirmed malaria in 1/39 of the BS-positive/mRDT-negative cases, and 6/14 of the BS-negative/mRDT-positive cases. The prevalence of confirmed malaria was 63/400 (15.8%). In multivariable logistic regression, malaria was associated with HIV (OR 3.45 [1.65-7.20], p=0.001). Current breastfeeding (OR 0.25 [0.11-0.56], p=0.001) and higher hemoglobin (OR 0.70 [0.60-0.81], p<0.001 per 1g/dL) were associated with decreased odds of malaria. Malaria parasite clearance was delayed in HIV-infected participants (p<0.001). Malaria is over-diagnosed even at referral centers in high transmission areas. Hospitalized HIV-infected children are more likely to have malaria and exhibit delayed clearance of parasites. Hospitals should consider using mRDTs as a first step for malaria testing among hospitalized children in sub-Saharan Africa.

High prevalence of Plasmodium falciparum pfcrt K76T mutation in children with sickle cell disease at a tertiary hospital in north-western Tanzania.

The high prevalence of sickle cell disease (SCD) and trait in Sub-Saharan Africa coincides with the distribution of Plasmodiumfalciparum malaria. Due to prolonged heavy use of chloroquine (CQ) as an antimalarial, drug resistance has developed. Many countries including Tanzania abandoned the use of CQ for uncomplicated malaria, except its use as prophylaxis in patients with sickle cell disease. This study investigated the prevalence of malaria in SCD patients and mutations associated with CQ resistance. Children diagnosed with sickle cell disease attending both outpatient clinic and those admitted at Bugando Medical Centre in northwestern Tanzania were screened for malaria using thick blood smear. A dried blood spot on Whatman filter paper was also taken for polymerase chain reaction (PCR) and restriction fragment length polymorphism. Among 123 known patients with sickle cell disease, the prevalence of malaria by blood smear microscopy was 3.2% and by PCR was 13.8%. The prevalence of K76T mutation among the patients was 81.3%. The majority of the patients (72.4%) were using chloroquine prophylaxis. In conclusion, the prevalence of malaria parasitaemia among children with sickle cell disease attending BMC is low (3.2%) by microscopy but several children maintain sub patent infection detectable by PCR. The prevalence of chloroquine resistant P falciparum in these children was higher than that previously seen in normal population in Tanzania. We recommend special attention to be paid to patients with sickle cell disease while studying the dynamics of drug resistant parasites.

Efficacy of artemether-lumefantrine in treatment of malaria among under-fives and prevalence of drug resistance markers in Igombe-Mwanza, north-western Tanzania.

BACKGROUND: Drug resistance to anti-malarials is a major public health problem worldwide. This study aimed at establishing the efficacy of artemether-lumefantrine (ACT) in Igombe-Mwanza, north-western Tanzania after a few years of ACT use, and establish the prevalence of mutations in key targets for artemisinin, chloroquine and sulphadoxine/pyrimetamine (SP) drugs. METHODS: A prospective single cohort study was conducted at Igombe health centre using artemether-lumefantrine combination therapy between February 2010 and March 2011. The follow-up period was 28 days and outcome measures were according to WHO guidelines. Blood was collected on Whatman filter paper for DNA analysis. DNA extraction was done using TRIS-EDTA method, and mutations in Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Pfatp6 were detected using PCR-RFLP methods established previously. RESULTS: A total of 103 patients completed the 28 days follow-up. The mean haemoglobin was 8.9 g/dl (range 5.0 to 14.5 g/dl) and mean parasite density was 5,608 parasites/µl. Average parasite clearance time was 34.7 hours and all patients cleared the parasites by day 3. There was no early treatment failure in this study. Late clinical failure was seen in three (2.9%) patients and late parasitological failure (LPF) was seen in two (1.9%). PCR-corrected LPF was 1% and adequate clinical and parasitological response was 96%. The majority of parasites have wild type alleles on pfcrt 76 and pfmdr1 86 positions being 87.8% and 93.7% respectively. Mutant parasites predominated at pfdhfr gene at the main three positions 108, 51 and 59 with prevalence of 94.8%, 75.3% and 82.5% respectively. Post-treatment parasites had more wild types of pfdhps at position 437 and 540 than pre-treatment parasites. No mutation was seen in pfatp6 769 in re-infecting or recrudescing parasites. CONCLUSION: The efficacy of artemether-lumefantrine for treatment of uncomplicated malaria is still high in the study area although the rate of re-infection is higher than previously reported. Parasite clearance after 48 hours was lower compared to previous studies. The prevalence of wild type allele pfcrt 76 K and pfmdr1 86 N was high in the study area while markers for SP resistance is still high. Artemether-lumefantrine may be selecting for wild type alleles on both positions (437 and 540) of pfdhps.

Large differences in prevalence of Pfcrt and Pfmdr1 mutations between Mwanza, Tanzania and Iganga, Uganda-a reflection of differences in policies regarding withdrawal of chloroquine?

BACKGROUND: Malaria is still a major public health problem in the world and sub-Saharan Africa is one of the most affected areas. Efforts to control malaria are highly affected by drug resistance to commonly used antimalarials. The introduction of artemisinin based combination therapy (ACT) as a first line drug seems to be a major step in treatment of uncomplicated malaria, though search for drugs to combine with artemisinins still continues. There have been reports on increased prevalence of the wild type markers Pfcrt 76K and Pfmdr1 86N in some African countries and ideas of using chloroquine (CQ) in intermittent presumptive treatment for adults (IPTa) is coming up. The common combination of artemether and lumefantrine even selects for parasites that are wild type at these positions. This study is comparing prevalence of mutation at these two positions in two East African countries with ACT as their first line drug but following somewhat different drug policies regarding CQ. In Tanzania CQ was stopped in 2001 but in Uganda CQ was retained in combination with sulfadoxine-pyrimethamine (SP) and used in home based management of fever for some time. SP is still used in IPT for pregnant women. METHODS: Blood smears and dried blood spots on Whatman filter papers were collected from 100 patients with uncomplicated malaria in Mwanza, Tanzania and 100 patients from Iganga, Uganda. DNA was extracted from all samples using Tris EDTA method. PCR and RFLP were performed and sequencing done on Pfcrt amplification products. RESULTS: The prevalence of K76T mutations at Pfcrt in samples from Mwanza, Tanzania was 40.5% (34/84) and 100% (100/100) in samples from Iganga, Uganda. Prevalence of N86Y mutations in Pfmdr1 was 16.9% (13/77) and 77.7% (63/81) in samples from Mwanza and Iganga, respectively. The re-emergence of CQ sensitive isolates in Mwanza, Tanzania showed the haplotype CVMNK typical for wild type isolates. CONCLUSIONS: The prevalence of CQ resistant parasites in Mwanza, Tanzania is low compared to the existing high level of resistant parasites in Iganga, Uganda. This could be an indication that CQ may become useful in the future in Tanzania. This study shows clearly that there is a difference in mutations at these positions in these two countries implementing similar but somewhat different drug policies. In Uganda the drug resistance has reached fixation while in Tanzania the prevalence is going down.

Outbreak of a novel Enterobacter sp. carrying blaCTX-M-15 in a neonatal unit of a tertiary care hospital in Tanzania.

Enterobacter hormaechei and Cronobacter sakazakii are amongst the most important causes of outbreaks of neonatal sepsis associated with powdered milk. In this study, we report for the first time an outbreak of a novel Enterobacter sp. harbouring bla(CTX-M-15) in a neonatal unit in Tanzania. Seventeen Gram-negative enteric isolates from neonatal blood cultures were studied. Antibiotic susceptibility was assessed by disc diffusion testing, and the presence of the bla(CTX-M-15) gene was established by polymerase chain reaction (PCR) and sequencing. Isolates were typed by pulsed-field gel electrophoresis (PFGE). Identification by biochemical profiling was followed by nucleotide sequencing of 16S ribosomal DNA (rDNA), rpoB and hsp60 alleles. Environmental sampling was done and control measures were established. Isolates were initially misidentified based on their fermentation characteristics and agglutination as Salmonella enterica serotype Paratyphi. All isolates were resistant to multiple antibiotics, except for ciprofloxacin and carbapenems, and were found to harbour bla(CTX-M-15) on a 291-kb narrow-range plasmid. PFGE analysis indicated the clonal outbreak of a single strain, infecting 17 neonates with a case fatality rate of 35%. The same strain was isolated from a milk bucket. Phylogenetic analysis using 16S rDNA, rpoB and hsp60 sequences permitted no definitive identification, clustering the strains in the Enterobacter cloacae complex with similarities of 92-98.8%. The data describe an outbreak of a novel bla(CTX-M-15)-positive, multiresistant Enterobacter strain in an African neonatal unit that can easily be misidentified taxonomically. These data highlight the need for constant surveillance of bacteria harbouring extended-spectrum ß-lactamases as well as improvements in hygiene measures in developing countries.